TRPC6特异性抑制剂SAR7334对宫颈癌细胞生物学行为影响的研究

doi:10.13418/j.issn.1001-165x.2020.06.010

中国临床解剖学杂志 ›› 2020, Vol. 38 ›› Issue (6): 674-679.doi: 10.13418/j.issn.1001-165x.2020.06.010

TRPC6特异性抑制剂SAR7334对宫颈癌细胞生物学行为影响的研究

蹇梦婵¹，　范丽²，　吴昀³，　史丹丹³，　卢敏³，　刘睿³，　贺细菊^3,4

1.湖北医药学院附属太和医院妇产科，湖北十堰 442000； 2.湖北医药学院附属人民医院妇产科，湖北十堰 442000；
3.湖北医药学院人体解剖学教研室，湖北十堰 442000； 4.湖北医药学院附属太和医院超声科，湖北十堰 442000

收稿日期:2020-01-18 出版日期:2020-11-25 发布日期:2020-12-08
通讯作者: 贺细菊，医学博士，硕士生导师，副教授，Tel：18071352919；E-mail：huizi630@163.com
作者简介:蹇梦婵（1993-），女，湖北十堰人，硕士研究生，主要从事妇科肿瘤研究，Tel：18772937410；E-mail：916170693@qq.com
基金资助:
湖北省教育厅重点项目（D20192103）；湖北医药学院人才启动金（2017QDJZR04）

Effect of TRPC6 inhibitor SAR7334 on biological behavior of cervical cancer

JIAN Meng-chan¹, FAN Li2, WU Yun³, SHI Dan-dan³, LU Min³, LIU Rui³, HE Xi-ju^3,4

1. Department of Obstetrics and Gynecology, Taihe Hospital，Hubei University of Medicine, Shiyan, Hubei, 42000, China; 2. Department of Obstetrics and Gynecology, Renmin Hospital, Hubei University of Medicine, Shiyan，Hubei, 442000, China; 3. Department of Anatomy, Hubei University of Medicine, Shiyan，Hubei, 442000, China; 4.Department of Ultrasonic, Taihe Hospital，Hubei University of Medicine, Shiyan, Hubei, 42000, China

Received:2020-01-18 Online:2020-11-25 Published:2020-12-08

摘要/Abstract

摘要： 目的　探讨TRPC6在宫颈癌组织中的表达及其抑制剂SAR7334对Siha（人宫颈鳞癌细胞）增殖和迁移的影响。方法　选取2017年9月至2019年9月在十堰市人民医院确诊为宫颈鳞癌的11例病例作为实验组，对照组取同一患者正常宫颈组织，免疫印迹法和免疫荧光法等检测宫颈组织中TRPC6蛋白表达；使用20、100、1000 nmol/L SAR7334处理Siha细胞，CCK8法和Hoechst染色检测细胞增殖与凋亡；划痕实验和Transwell法验检测细胞迁移。免疫印迹法检测TRPC6通道阻断后Siha细胞自噬程度的改变。结果　宫颈癌组织中TRPC6表达上调；与对照组相比，用100 nmol/L SAR7334阻断TRPC6后，Siha细胞的增殖和迁移减少，划痕愈合率降低，凋亡率增加（P<0.05）。TRPC6通道阻断后，Siha细胞自噬减弱。结论　TRPC6在宫颈癌中表达上调，其抑制剂SAR7334可能通过影响细胞自噬抑制宫颈癌Siha细胞的增殖与迁移。

关键词: TRPC6, 　SAR7334, 　宫颈癌Siha细胞, 　细胞自噬

Abstract: Objective　To investigate the expression of TRPC6 in cervical cancer and the effect of its inhibitor SAR7334 on the proliferation and migration of Siha （Human cervical squamous cell carcinoma cell）.　Methods　Eleven cases of cervical squamic carcinoma diagnosed in People’s hospital of Shiyan from September 2017 to September 2019 were selected as the experimental group. Normal cervical tissue of the same patient was used as the control group. Western-blot and immunofluorescence were used to detect the expression of TRPC6; Siha cells were treated with 20, 100, 1000 nmol/L SAR7334, cell proliferation and apoptosis were detected by CCK8 method and Hoechst staining. Cell migration was detected by scratch test and Transwell test. After TRPC6 channel was blocked, the change of autophagy in Siha cells was detected by immunoblotting.　Results　The expression of TRPC6 protein in cervical cancer tissues was significantly higher than that of normal tissues. Compared with the control group, after blocking TRPC6 with 100 nmol/L SAR7334, the proliferation and migration of Siha cells reduced, the scratch healing rate reduced, and the apoptosis rate increased (P<0.05). After the TRPC6 channel was blocked, the autophagy of Siha cell weakened.　Conclusions　The expression of TRPC6 is up-regulated in cervical cancer, and its inhibitor SAR7334 may inhibit the proliferation and migration of cervical cancer Siha cells by affecting cell autophagy.

Key words: , TRPC6；　SAR7334；　Cervical cancer Siha cells；　Autophagy

中图分类号:

R737.33

蹇梦婵, 范丽, 吴昀, 史丹丹, 卢敏, 刘睿, 贺细菊. TRPC6特异性抑制剂SAR7334对宫颈癌细胞生物学行为影响的研究[J]. 中国临床解剖学杂志, 2020, 38(6): 674-679.

JIAN Meng-chan, FAN Li, WU Yun, SHI Dan-dan, LU Min, LIU Rui, HE Xi-ju. Effect of TRPC6 inhibitor SAR7334 on biological behavior of cervical cancer [J]. Chinese Journal of Clinical Anatomy, 2020, 38(6): 674-679.

参考文献 22

[1]	Prevarskaya N, Skryma R, Shuba Y. Ion channels in cancer: are cancer hallmarks oncochannelopathies?[J]. Physiol Rev, 2018, 98(2):559-621.
[2]	Wan Q, Zheng A, Liu X, et al. Expression of transient receptor potential channel 6 in cervical cancer[J]. Onco Targets Ther, 2012, 5:171-176.
[3]	Montell C, Birnbaumer L, Flockerzi V. The TRP channels, a remarkably functional family[J]. Cell, 2002, 108(5):595-598.
[4]	Cheng HP, Wei S, Wei LP, et al. Calcium signaling in physiology and pathophysiology[J]. Acta Pharmacol Sin, 2006, 27(7):767-772.
[5]	Cai R, Ding X, K Z. Blockade of TRPC6 channels induced G2/M phase arrest and suppressed growth in human gastric cancer cells [J]. Int J Cancer, 2009, 125(10):2281-2287.
[6]	Song Y, Liu G, Liu S, et al. Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion[J]. Onco Targets Ther, 2019,12:5269-5279.
[7]	Ding X, He Z, Shi Y, et al. Targeting TRPC6 channels in oesophageal carcinoma growth[J]. Expert Opin Ther Targets, 2010, 14(5):513-527.
[8]	Zhang Y, Zhang Y, Fan H, et al. Study on the role of transient receptor potential C6 channels in esophageal squamous cell carcinoma radiosensitivity[J]. J Thorac Dis, 2017, 9(10):3802-3809.
[9]	Bernichtein S, Pigat N, Barry Delongchamps N, et al. Vitamin D3 prevents calcium-induced progression of early-stage prostate tumors by counteracting TRPC6 and calcium sensing receptor upregulation[J]. Cancer Res, 2017, 77(2):355-365.
[10]	Thebault S, Flourakis M, Vanoverberghe K, et al. Differential role of transient receptor potential channels in Ca2+ entry and proliferation of prostate cancer epithelial cells[J]. Cancer Res, 2006, 66(4):2038-2047.
[11]	Ding X, He Z, Zhou K, et al. Essential role of TRPC6 channels in G2/M phase transition and development of human glioma[J]. J Natl Cancer Inst, 2010,102(14):1052-1068.
[12]	Diez-Bello R, Jardin I, Lopez JJ, et al. (-)‑Oleocanthal inhibits proliferation and migration by modulating Ca entry through TRPC6 in breast cancer cells[J]. Biochim Biophys Acta Mol Cell Res, 2019,1866(3):474-485.
[13]	Jardin I, Diez-Bello R, Lopez JJ, et al. TRPC6 channels are required for proliferation, migration and invasion of breast cancer cell lines by modulation of Orai1 and Orai3 surface exposure[J]. Cancers (Basel), 2018, 10(9):331.
[14]	Kim JH, Hwang KH, Eom M, et al. WNK1 promotes renal tumor progression by activating TRPC6-NFAT pathway[J]. FASEB J, 2019, 33(7):8588-8599.
[15]	Zeng B, Yuan C, Yang X, et al. TRPC channels and their splice variants are essential for promoting human ovarian cancer cell proliferation and tumorigenesis[J]. Curr Cancer Drug Targets, 2013,13(1):103-116.
[16]	王朕华，张珂，王悦, 等. TRPC6在子宫内膜癌组织中的表达及对细胞增殖作用的研究[J]. 中国实用妇科与产科杂志, 2019, 35(5):569-573.
[17]	王朕华，井佳雨，王悦, 等. 阻断TRPC6通道对人子宫内膜癌细胞和裸鼠移植瘤放射敏感性的影响[J]. 现代妇产科进展, 2019, 28(5):346-349.
[18]	Aydar E, Yeo S, Djamgoz M, et al. Abnormal expression, localization and interaction of canonical transient receptor potential ion channels in human breast cancer cell lines and tissues: a potential target for breast cancer diagnosis and therapy [J]. Cancer Cell Int, 2009, 9(23):1-12.
[19]	El Boustany C, Bidaux G, Enfissi A, et al. Capacitative calcium entry and transient receptor potential canonical 6 expression control human hepatoma cell proliferation[J]. Hepatology, 2008, 47(6):2068-2077.
[20]	Tian Y, Zhu MX. A novel TRPC6-dependent mechanism of TGF-β-induced migration and invasion of human hepatocellular carcinoma cells[J]. Sci China Life Sci, 2018, 61(9):1120-1122.
[21]	Hou X, Xiao H, Zhang Y, et al. Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation[J]. Cell Death Dis, 2018, 9(10):1015.
[22]	Peixoto P, Grandvallet C, Feugeas JP, et al. Epigenetic control of autophagy in cancer cells: a key process for cancer-related phenotypes[J]. Cells, 2019, 8(12):1656.

TRPC6特异性抑制剂SAR7334对宫颈癌细胞生物学行为影响的研究

Effect of TRPC6 inhibitor SAR7334 on biological behavior of cervical cancer

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