코미팜

대만 의료진 코미녹스 구강암 논문 발표 발췌

21/03/27 19:21
조회 779

gregory16 자기 소개가 없습니다.

Arsenic compounds activate the MAPK and caspase pathways to induce apoptosis in OEC？M1 gingival epidermal carcinoma

Authors:
- Ning？Ping Foo
- Chi？Lin Ko
- Chiao？Yun Chu
- Chia？Yih Wang
- Edmund Cheung So
- Bu？Miin Huang
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Affiliations: Department of Emergency Medicine, An Nan Hospital, China Medical University, Tainan 70965, Taiwan, R.O.C., Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C., Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan 71101, Taiwan, R.O.C.

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Published online on: October 7, 2020 https://doi.org/10.3892/or.2020.7793
Pages: 2701-2714

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Abstract

Arsenic is a well？documented environmental toxicant that can induce neurotoxicity and peripheral vascular diseases. In fact, arsenic trioxide has been used to treat various cancer types. Oral cancer has been in the top ten common cancers for decades in Taiwan, and the incidence rate is continuously increasing. The majority of oral cancers

are associated with excessive tobacco, alcohol consumption and betel chewing. To the best of our knowledge, no study has revealed the effect of arsenic compounds on oral cancers. Thus, the present study used OEC？M1 oral squamous carcinoma cells treated with sodium arsenite (NaAsO2) and dimethylarsenic acid (DMA) to determine whether both arsenic compounds could exert anticancer effects on oral cancer. The results demonstrated that NaAsO2 and DMA induced rounding up and membrane blebbing in OEC？M1 cells, which are morphological characteristics of apoptosis. Annexin V/PI double staining analysis further confirmed that both arsenic compounds induced apoptosis of OEC？M1 cells. In addition, NaAsO2 and DMA significantly decreased the survival rate and increased the percentage of OEC？M1 cells in the subG1 and G2/M phases (P<0.05). Furthermore, both arsenic compounds significantly activated the cleavage of caspase？8, ？9, ？3 and PARP, and the phosphorylation of JNK, ERK1/2 and p38 in OEC？M1 cells (P<0.05). Collectively, the findings of the present study indicated that NaAsO2 and DMA stimulate extrinsic and intrinsic apoptotic pathways through the activation of the MAPK pathways to induce apoptosis of OEC？M1 cells, suggesting that NaAsO2 and DMA may be used as novel anticancer drugs for oral cancers.

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1	David MC, Randal SW and Stephen YL: Head and neck cancer. Cancer. 113 (Suppl 7):S1911？S1932. 2008. View Article : Google Scholar
2	Laraway DC, Lakshmiah R, Lowe D, Roe B and Rogers SN: Quality of life in older people with oral cancer. Br J Oral Maxillofac Surg. 50:715？720. 2012. View Article : Google Scholar : PubMed/NCBI
3	Sudbø J: Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 345:376？377. 2001. View Article : Google Scholar
4	Ko YC, Huang YL, Lee CH, Chen MJ, Lin LM and Tsai CC: Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med. 24:450？453. 1995. View Article : Google Scholar : PubMed/NCBI
5	Bernier J and Cooper JS: Chemoradition after surgery for high-risk head and neck cancer patients: How strong is the evidence? Oncologist. 10:215？224. 2005. View Article : Google Scholar : PubMed/NCBI
6	Chen CJ, You SL, Lin LH, Hsu WL and Yang YW: Cancer epidemiology and control in Taiwan: A brief review. Jpn J Clin Oncol. 32 (Suppl):S66？S81. 2002. View Article : Google Scholar : PubMed/NCBI
7	Mandal BK and Suzuki KT: Arsenic round the world: A review. Talanta. 58:201？235. 2002. View Article : Google Scholar : PubMed/NCBI
8	Calatayud M, Devesa V and V？lez D: Differential toxicity and gene expression in Caco-2 cells exposed to arsenic species. Toxicol Lett. 218:70？80. 2013. View Article : Google Scholar : PubMed/NCBI
9	Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, et al: Use of arsenic trioxide (As₂O₃) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood. 89:3354？3360. 1997. View Article : Google Scholar : PubMed/NCBI
10	Yedjou C, Tchounwou P, Jenkins J and McMurray R: Basic mechanisms of arsenic trioxide (ATO)-induced apoptosis in human leukemia (HL-60) cells. J Hematol Oncol. 3:282010. View Article : Google Scholar : PubMed/NCBI
11	Liu Q, Hilsenbeck S and Gazitt Y: Arsenic trioxide-induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL. Blood. 101:4078？4087. 2003. View Article : Google Scholar : PubMed/NCBI
12	Mandegary A, Torshabi M, Seyedabadi M, Amirheidari B, Sharif E and Ghahremani MH: Indomethacin-enhanced anticancer effect of arsenic trioxide in A549 cell line: Involvement of apoptosis and phospho-ERK and p38 MAPK pathways. Biomed Res Int. 2013:2375432013. View Article : Google Scholar : PubMed/NCBI
13	Wang HY, Zhang B, Zhou JN, Wang DX, Xu YC, Zeng Q, Jia YL, Xi JF, Nan X, He LJ, et al: Arsenic trioxide inhibits liver cancer stem cells and metastasis by targeting SRF/MCM7 complex. Cell Death Dis. 10:4532019. View Article : Google Scholar : PubMed/NCBI
14	Kim EY, Lee SS, Shin JH, Kim SH, Shin DH and Baek SY: Anticancer effect of arsenic trioxide on cholangiocarcinoma: In vitro experiments and in vivo xenograft mouse model. Clin Exp Med. 14:215？224. 2014. View Article : Google Scholar : PubMed/NCBI
15	Mu YF, Chen YH, Chang MM, Chen YC and Huang BM: Arsenic compounds induce apoptosis through caspase pathway activation in MA-10 Leydig tumor cells. Oncol Lett. 18:944？954. 2019.PubMed/NCBI
16	Byun JM, Lee DS, Landen CN, Kim DH, Kim YN, Lee KB, Sung MS, Park SG and Jeong DH: Arsenic trioxide and tetraarsenic oxide induce cytotoxicity and have a synergistic effect with cisplatin in paclitaxel-resistant ovarian cancer cells. Acta Oncol. 58:1594？1602. 2019. View Article : Google Scholar : PubMed/NCBI
17	Kim MJ, Jung JH, Lee WS, Yun JW, Lu JN, Yi SM, Kim HJ, Chang SH, Kim GS, Hong SC and Ha WS: Arsenic hexoxide enhances TNF-α-induced anticancer effects by inhibiting NF-κB activity at a safe dose in MCF-7 human breast cancer cells. Oncol Rep. 31:2305？2311. 2014. View Article : Google Scholar : PubMed/NCBI
18	Nagappan A, Lee WS, Yun JW, Lu JN, Chang SH, Jeong JH, Kim GS, Jung JM and Hong SC: Tetraarsenic hexoxide induces G2/M arrest, apoptosis, and autophagy via PI3K/Akt suppression and p38 MAPK activation in SW620 human colon cancer cells. PLoS One. 12:e01745912017. View Article : Google Scholar : PubMed/NCBI
19	Mann KK, Wallner B, Lossos IS and Miller WH Jr: Darinaparsin: A novel organic arsenical with promising anticancer activity. Expert Opin Investig Drugs. 18:1727？1734. 2009. View Article : Google Scholar : PubMed/NCBI
20	Cheng X, Quint？s-Cardama A, Golemovic M, Zingaro R, Gao MZ, Freireich EJ, Andreeff M, Kantarjian HM and Verstovsek S: The organic arsenic derivative GMZ27 induces PML-RARα-independent apoptosis in myeloid leukemia cells. Anticancer Res. 32:2871？2880. 2012.PubMed/NCBI
21	Kasibhatla S and Tseng B: Why target apoptosis in cancer treatment? Mol Cancer Ther. 2:573？580. 2003.PubMed/NCBI
22	D'Arcy MS: Cell death: A review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 43:582？592. 2019. View Article : Google Scholar : PubMed/NCBI
23	Ashkenazi A and Dixit VM: Death receptors: Signaling and modulation. Science. 281:1305？1308. 1998. View Article : Google Scholar : PubMed/NCBI
24	Akao Y, Nakagawa Y and Akiyama K: Arsenic trioxide induces apoptosis in neuroblastoma cell lines through the activation of caspase 3 in vitro. FEBS Lett. 455:59？62. 1999. View Article : Google Scholar : PubMed/NCBI
25	Chen GQ, Zhu J, Shi XG, Ni JN, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, et al: In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As₂O₃) in the treatment of acute promyelocytic leukemia: As₂O₃ induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR/PML proteins. Blood. 88:1052？1061. 1996. View Article : Google Scholar : PubMed/NCBI
26	You Z, Liu SP, Du J, Wu YH and Zhang SZ: Advancements in MAPK signaling pathways and MAPK-targeted therapies for ameloblastoma: A review. J Oral Pathol Med. 48:201？205. 2019. View Article : Google Scholar : PubMed/NCBI
27	Wada T and Penninger JM: Mitogen-activated protein kinases in apoptosis regulation. Oncogene. 23:2838？2849. 2004. View Article : Google Scholar : PubMed/NCBI
28	Hayakawa J, Ohmichi M, Kurachi H, Ikegami H, Kimura A, Matsuoka T, Jikihara H, Mercola D and Murata Y: Inhibition of extracellular signal-regulated protein kinase or c-Jun N-terminal protein kinase cascade, differentially activated by cisplatin, sensitizes human ovarian cancer cell line. J Biol Chem. 274:31648？31654. 1999. View Article : Google Scholar : PubMed/NCBI
29	Kang YH and Lee SJ: The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells. J Cell Physiol. 217:23？33. 2008. View Article : Google Scholar : PubMed/NCBI
30	Yang CY and Meng CL: Regulation of PG synthase by EGF and PDGF in human oral, breast, stomach, and fibrosarcoma cancer cell lines. J Dent Res. 73:1407？1415. 1994. View Article : Google Scholar : PubMed/NCBI
31	Wong DY, Chang KW, Chen CF and Chang RC: Characterization of two new cell lines derived from oral cavity human squamous cell carcinomas-OC1 and OC2. J Oral Maxillofac Surg. 48:385？390. 1990. View Article : Google Scholar : PubMed/NCBI
32	Wu WC, Hsiao JR, Lian YY, Lin CY and Huang BM: The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line. Cancer Chemother Pharmacol. 60:103？111. 2007. View Article : Google Scholar : PubMed/NCBI
33	Kang FC, Wang SC, So EC, Chang MM, Wong KL, Cheng KS, Chen YC and Huang BM: Propofol may increase caspase and MAPK pathways, and suppress the Akt pathway to induce apoptosis in MA-10 mouse Leydig tumor cells. Oncol Rep. 41:3565？3574. 2019.PubMed/NCBI
34	Kang FC, Chen YC, Wang SC, So EC and Huang BM: Propofol induces apoptosis by activating caspases and the MAPK pathways, and inhibiting the Akt pathway in TM3 mouse Leydig stem/progenitor cells. Int J Mol Med. 46:439？448. 2020.PubMed/NCBI
35	Lowry OH, Rosebrough NJ, Farr AL and Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem. 193:265？275. 1951.PubMed/NCBI
36	Chang MM, Lai MS, Hong SY, Pan BS, Huang H, Yang SH, Wu CC, Sun HS, Chuang JI, Wang CY and Huang BM: FGF9/FGFR2 increase cell proliferation by activating ERK1/2, Rb/E2F1, and cell cycle pathways in mouse Leydig tumor cells. Cancer Sci. 109:3503？3518. 2018. View Article : Google Scholar : PubMed/NCBI
37	Chang MM, Pan BS, Wang CY and Huang BM: Cordycepin-induced unfolded protein response-dependent cell death, and AKT/MAPK-mediated drug resistance in mouse testicular tumor cells. Cancer Med. 8:3949？3964. 2019. View Article : Google Scholar : PubMed/NCBI
38	van Engeland M, Ramaekers FC, Schutte B and Reutelingsperger CP: A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture. Cytometry. 24:131？139. 1996. View Article : Google Scholar : PubMed/NCBI
39	Li W and Chou IN: Effects of sodium arsenite on the cytoskeleton and cellular glutathione levels in cultured cells. Toxicol Appl Pharmacol. 114:132？139. 1992. View Article : Google Scholar : PubMed/NCBI
40	Ochi T, Nakajimar F and Fukumori N: Different effects of inorganic and dimethylated arsenic compounds on cell morphology, cytoskeletal organization, and DNA synthesis in cultured Chinese hamster V79 cells. Arch Toxicol. 72:566？573. 1998. View Article : Google Scholar : PubMed/NCBI
41	Zuk A, Targosz-Korecka M and Szymonski M: Effect of sel ected drugs used in asthma treatment on morphology and elastic properties of red blood cells. Int J Nanomedicine. 6:249？57. 2011. View Article : Google Scholar : PubMed/NCBI
42	Vahter M: Methylation of inorganic arsenic in different mammalian species and population groups. Sci Prog. 82:69？88. 1999. View Article : Google Scholar : PubMed/NCBI
43	Lin KW, Behl S, Furst A, Chien P and Toia RF: Formation of dimethylarsinic acid from methylation of sodium arsenite in lumbricus terrestris. Toxicol In Vitro. 12:197？199. 1998. View Article : Google Scholar : PubMed/NCBI
44	Hartwell LH and Weinert TA: Checkpoints: Controls that ensure the order of cell cycle events. Science. 246:629？634. 1989. View Article : Google Scholar : PubMed/NCBI
45	Yih LH, Wu YC, Hsu NC and Kuo HH: Arsenic trioxide induces abnormal mitotic spindles through a PIP4KIIγ/Rho pathway. Toxicol Sci. 128:115？125. 2012. View Article : Google Scholar : PubMed/NCBI
46	Ling YH, Jiang JD, Holland JF and Perez-Soler R: Arsenic trioxide produces polymerization of microtubules and mitotic arrest before apoptosis in human tumor cell lines. Mol Pharmacol. 62:529？538. 2002. View Article : Google Scholar : PubMed/NCBI
47	Concin N, Stimpfl M, Zeillinger C, Wolff U, Hefler L, Sedlak J, Leodolter S and Zeillinger R: Role of p53 in G2/M cell cycle arrest and apoptosis in response to gamma-irradiation in ovarian carcinoma cell lines. Int J Oncol. 22:51？57. 2003.PubMed/NCBI
48	Shu CH, Yang WK, Shih YL, Kuo ML and Huang TS: Cell cycle G2/M arrest and activation of cyclin-dependent kinases associated with low-dose paclitaxel-induced sub-G1 apoptosis. Apoptosis. 2:463？470. 1997. View Article : Google Scholar : PubMed/NCBI
49	Tyagi AK, Singh RP, Agarwal C, Chan DC and Agarwal R: Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis. Clin Cancer Res. 8:3512？3519. 2002.PubMed/NCBI
50	Brown JM and Attardi LD: The role of apoptosis in cancer development and treatment response. Nat Rev Cancer. 5:231？237. 2005. View Article : Google Scholar : PubMed/NCBI
51	Fan TJ, Han LH, Cong RS and Liang J: Caspase family proteases and apoptosis. Acta Biochim Biophys Sin (Shanghai). 37:719？727. 2005. View Article : Google Scholar : PubMed/NCBI
52	Cheng B, Yang X, Han Z, An L and Liu S: Arsenic trioxide induced the apoptosis of laryngeal cancer via down-regulation of survivin mRNA. Auris Nasus Larynx. 35:95？101. 2008. View Article : Google Scholar : PubMed/NCBI
53	Jiang XH, Wong BC, Yuen ST, Jiang SH, Cho CH, Lai KC, Lin MC, Kung HF and Lam SK: Arsenic trioxide induces apoptosis in human gastric cancer cells through up-regulation of p53 and activation ofcaspase-3. Int J Cancer. 91:173？179. 2001. View Article : Google Scholar : PubMed/NCBI
54	Wu X, Shi J, Wu Y, Tao Y, Hou J, Meng X, Hu X, Han Y, Jiang W, Tang S, et al: Arsenic trioxide-mediated growth inhibition of myeloma cells is associated with an extrinsic or intrinsic signaling pathway through activation of TRAIL or TRAIL receptor 2. Cancer Biol Ther. 10:1201？1214. 2010. View Article : Google Scholar : PubMed/NCBI
55	Binet F, Chiasson S and Girard D: Evidence that endoplasmic reticulum (ER) stress and caspase-4 activation occur in human neutrophils. Biochem Biophys Res Commun. 391:18？23. 2010. View Article : Google Scholar : PubMed/NCBI
56	Lunghi P, Giuliani N, Mazzera L, Lombardi G, Ricca M, Corradi A, Cantoni AM, Salvatore L, Riccioni R, Costanzo A, et al: Targeting MEK/MAPK signal transduction module potentiates ATO-induced apoptosis in multiple myeloma cells through multiple signaling pathways. Blood. 112:2450？2462. 2008. View Article : Google Scholar : PubMed/NCBI
57	Kircelli F, Akay C and Gazitt Y: Arsenic trioxide induces p53-dependent apoptotic signals in myeloma cells with SiRNA-silenced p53: MAP kinase pathway is preferentially activated in cells expressing inactivated p53. Int J Oncol. 30:993？1001. 2007.PubMed/NCBI
58	Lam HK, Li K, Chik KW, Yang M, Liu VC, Li CK, Fok TF, Ng PC, Shing MM, Chuen CK and Yuen PM: Arsenic trioxide mediates intrinsic and extrinsic pathways of apoptosis and cell cycle arrest in acute megakaryocytic leukemia. Int J Oncol. 27:537？545. 2005.PubMed/NCBI
59	Ivanov VN and Hei TK: Regulation of apoptosis in human melanoma and neuroblastoma cells by statins, sodium arsenite and TRAIL: A role of combined treatment versus monotherapy. Apoptosis. 16:1268？1284. 2011. View Article : Google Scholar : PubMed/NCBI
60	Shen L and Zhang G, Lou Z, Xu G and Zhang G: Cryptotanshinone enhances the effect of Arsenic trioxide in treating liver cancer cell by inducing apoptosis through downregulating phosphorylated- STAT3 in vitro and in vivo. BMC Complement Altern Med. 17:1062017. View Article : Google Scholar : PubMed/NCBI
61	Wang X and Zhang M: Synergistic effects of valproic acid and arsenic trioxide on RPMI8226 cells in vitro and the possible underlying mechanisms. Mol Med Rep. 12:1449？1456. 2015. View Article : Google Scholar : PubMed/NCBI
62	Amr？n D, S？nchez Y, Fern？ndez C, Ramos AM, de Blas E, Br？ard J, Calle C and Aller P: Arsenic trioxide sensitizes promonocytic leukemia cells to TNFalpha-induced apoptosis via p38-MAPK-regulated activation of both receptor-mediated and mitochondrial pathways. Biochim Biophys Acta. 1773:1653？1663. 2007. View Article : Google Scholar : PubMed/NCBI
63	Alvarado-Kristensson M, Melander F, Leandersson K, R？nnstrand L, Wernstedt C and Andersson T: p38-MAPK signals survival by phosphorylation of caspase-8 and caspase-3 in human neutrophils. J Exp Med. 199:449？458. 2004. View Article : Google Scholar : PubMed/NCBI
64	Grethe S, Ares MP, Andersson T and P？rn-Ares MI: p38 MAPK mediates TNF-induced apoptosis in endothelial cells via phosphorylation and downregulation of Bcl-x(L). Exp Cell Res. 298:632？642. 2004. View Article : Google Scholar : PubMed/NCBI
65	Choi WS, Eom DS, Han BS, Kim WK, Han BH, Choi EJ, Oh TH, Markelonis GJ, Cho JW and Oh YJ: Phosphorylation of p38 MAPK induced by oxidative stress is linked to activation of both caspase-8- and ？9-mediated apoptotic pathways in dopaminergic neurons. J Biol Chem. 279:20451？2060. 2004. View Article : Google Scholar : PubMed/NCBI
66	Falchi L, Verstovsek S, Ravandi-Kashani F and Kantarjian HM: The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy. Cancer. 122:1160？1168. 2016. View Article : Google Scholar : PubMed/NCBI
67	Torka P, Al Ustwani O, Wetzler M, Wang ES and Griffiths EA: Swallowing a bitter pill-oral arsenic trioxide for acute promyelocytic leukemia. Blood Rev. 30:201？211. 2016. View Article : Google Scholar : PubMed/NCBI

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비소성분들은 MAPK와 Caspase 경로를 활성화하여 OEC-M1 생강 표피암에 세포자멸을 유도합니다

비소는 신경 독성 및 말초 혈관 질환을 유발할 수있는 잘 문서화 된 환경 독성 물질입니다.

사실, 삼산화 비소는 다양한 암 유형을 치료하는 데 사용되었습니다.

구강암은 대만에서 수십 년 동안 10 대 흔한 암에 속했으며 발병률은 지속적으로 증가하고 있습니다.

대부분의 구강암은 과도한 담배, 음주 및 빈랑 씹기와 관련이 있습니다.

우리가 아는 한, 비소 화합물이 구강암에 미치는 영향을 밝혀낸 연구는 없습니다.

따라서 현재 연구에서는 비소 화합물 (NaAsO2)과 디메틸 비 소산 (DMA)으로 처리 된 OEC？M1 구강 편평 암종 세포를 사용하여 두 비소 화합물이 모두 구강암에 항암 효과를 나타낼 수 있는지 여부를 결정했습니다.

결과는 NaAsO2 및 DMA가 OEC？M1 세포에서 반올림 및 막 블 리빙을 유도하고, 세포 사멸의 형태 학적 특성입니다. Annexin V / PI 이중 염색 분석은 두 비소 화합물이 OEC？M1 세포의 세포 사멸을 유도한다는 것을 추가로 확인했습니다.

또한 NaAsO2와 DMA는 subG1 및 G2 / M 단계에서 생존율을 현저히 감소시키고 OEC？M1 세포의 비율을 증가 시켰습니다 (P <0.05). 또한 두 비소 화합물 모두 OEC？M1 세포에서 caspase？8, ？9, ？3 및 PARP의 절단과 JNK, ERK1 / 2 및 p38의 인산화를 크게 활성화했습니다

(P <0.05). 총체적으로, 본 연구의 결과는 NaAsO2와 DMA가 MAPK 경로의 활성화를 통해 외인성 및 내인성 아폽토시스 경로를 자극하여 OEC？M1 세포의 아폽토시스를 유도하는 것으로 나타 났으며, 이는 NaAsO2 및 DMA가 구강암에 대한 새로운 항암제로 사용될 수 있음을 시사합니다. .

Annexin V / PI 이중 염색 분석은 두 비소 화합물이 OEC？M1 세포의 세포 사멸을 유도한다는 사실을 추가로 확인했습니다. 또한 NaAsO2와 DMA는 subG1 및 G2 / M 단계에서 생존율을 현저히 감소시키고 OEC？M1 세포의 비율을 증가 시켰습니다 (P <0.05). 또한 두 비소 화합물 모두 OEC？M1 세포에서 caspase？8, ？9, ？3 및 PARP의 절단과 JNK, ERK1 / 2 및 p38의 인산화를 크게 활성화했습니다

(P <0.05). 총체적으로, 본 연구의 결과는 NaAsO2와 DMA가 MAPK 경로의 활성화를 통해 외인성 및 내인성 아폽토시스 경로를 자극하여 OEC？M1 세포의 아폽토시스를 유도하는 것으로 나타 났으며, 이는 NaAsO2 및 DMA가 구강암에 대한 새로운 항암제로 사용될 수 있음을 시사합니다.

. Annexin V / PI 이중 염색 분석은 두 비소 화합물이 OEC？M1 세포의 세포 사멸을 유도한다는 사실을 추가로 확인했습니다.