阻断磷脂酶C-γ1信号通路对大肠癌细胞凋亡的影响

南方医科大学学报 ›› 2005, Vol. 25 ›› Issue (02): 177-180.

阻断磷脂酶C-γ1信号通路对大肠癌细胞凋亡的影响

刘俊, 李明, 曾位森, 白晓春, 罗深秋

南方医科大学细胞生物学教研室, 广东, 广州, 510515

出版日期:2005-02-20 发布日期:2005-02-20
基金资助:
收稿日期:2004-10-8。
基金项目:广东省自然科学基金(020015);全军医药卫生科研基金(01MB098)
作者简介:刘俊(1980- ),男,在读硕士研究生,电话:020-61648207,E-mail:looselj@fimmu.com
通讯作者:罗深秋(1955- ),教授,博士研究生导师,电话:020-61648208,E-mail:luoshq888@163.com

Inhibition of phospholipase C gamma1 signaling pathway promotes apoptosis of human

LIU Jun, LI Ming, ZENG Wei-sen, BAI Xiao-chun, LUO Shen-qiu

南方医科大学细胞生物学教研室, 广东, 广州, 510515

Online:2005-02-20 Published:2005-02-20

摘要/Abstract

摘要： 目的探讨磷脂酶C-γ1(PLC-γ1)信号通路被阻断对大肠癌细胞凋亡状态的影响。方法利用U73122(1、5、10μmol/L)处理细胞以阻断PLC-γ1信号通路,光镜、电镜观察细胞形态改变,MTT法评估细胞杀伤效应,流式细胞仪分析凋亡细胞比例。结果 PLC-γ1信号通路阻断后,大肠癌细胞出现了典型的凋亡形态学改变,存活细胞明显减少,流式细胞仪检测出现典型的凋亡亚二倍体峰,凋亡细胞所占比例达到半数以上。结论阻断PLC-γ1信号通路能够启动大肠癌细胞凋亡。

Abstract: Objective To investigate the effects of inhibiting phospholipase C gamma1 signaling pathway on the apoptosis of human colorectal carcinoma cells. Methods SW620 cells were treated with U73122 in vitro to inhibit the phospholipase C gamma1 signalling pathway and examined under light microscope and transmission electron microscope for analyzing changes in apoptotic behavior of the cells. MTT assay was used to evaluate the cell killing effects, and the percentage of apoptotic cells analyzed using flow cytometry. Results After inhibition of the phospholipase C gamma1 signaling pathway by U73122, SW620 cells exhibited obvious apoptotic morphology, the viable cells decreased dramatically, and the percentage of apoptotic cells rose to above 50%. Conclusion Inhibition of phospholipase C gamma1 signaling pathway can induce apoptosis of human colorectal carcinoma cells.

中图分类号:

刘俊, 李明, 曾位森, 白晓春, 罗深秋. 阻断磷脂酶C-γ1信号通路对大肠癌细胞凋亡的影响[J]. 南方医科大学学报, 2005, 25(02): 177-180.

LIU Jun, LI Ming, ZENG Wei-sen, BAI Xiao-chun, LUO Shen-qiu. Inhibition of phospholipase C gamma1 signaling pathway promotes apoptosis of human[J]. Journal of Southern Medical University, 2005, 25(02): 177-180.

参考文献

[1] Deb TB, Coticchia CM, Dickson RB, et al. Calmodulin-mediated activation of Akt(PKB) regulates survival of c-Myc-overexpressing mouse mammary carcinoma cells[J]. J Biol Chem, 2004, 279(37):38903-11.
[2] JiQS, WinnierGE, NiswenderKD, etal. Essential role of the tyrosine kinase substrate phospholipase C gammal in mammalian growth and development[J]. Proc Natl Acad Sci USA, 1997, 94(7):2999-3003.
[3] Liao HJ, Kume T, Mckay C, et al. Absence of erythrogenesis and vasculogenesis in phospholipase c gammal deficient mice [J]. J Biol Chem, 2002, 277(11): 9335-41.
[4] LeeYH, KimS, Kim J, et al. Overexpressionofphospholipase C-gammal suppresses UVC-induced apoptosis through inhibition of c-fos accumulation and c-Jun N-terminal kinase activation in PC12 cells[J]. Biochim Biophys Acta, 1999, 1440(2-3): 235-43.
[5] Bai XC, Liu AL, Deng F, et al. Phospholipase C-gammal is required for survival in heat stress: involvement of protein kinase C-dependent Bcl-2 phosphorylation [J]. J Biochem, 2002, 131(2): 207-12.
[6] Park DI, Choi HY, Kam CW, et al. Wikyungtang inhibits proliferation of A549 human lung cancer cells via inducing apoptosis and suppressing cyclooxygenase-2 activity [J]. Oncol Rep, 2004, 11(4): 853-6.
[7] Woo JH, Kim YH, Choi YJ, et al. Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release ofcytochrome c and inhibition ofAkt [J].Carcinogenesis, 2003, 24(7): 1199-208.
[8] Yeo JK, Cha SD, Cho CH, et al. Se-methylselenocysteine induces apoptosis through caspase activation and Bax cleavage mediated by calpain in SKOV-3 ovarian cancer cells [J]. Cancer Lett, 2002, 182(1): 83-92.
[9] Noh DY, Lee YH, Kim SS, et al. Elevated content ofphospholipase C-gamma 1 in colorectal cancer[J]. Cancer, 1994, 73(1): 36-41.
[10] Smith MR, Lin YL, Kim H, et al. Inhibition of serum-and rasstimulated DNA synthesis by antibodies to phospholipase C [J]. Science, 1990, 247(4946): 1074-7.
[11] Mario J, Rebecchi BP, Srinivas N, et al. Structure, function, and control ofphosphoinositide-specific phospholipase C [J]. Physiol Rev, 2000, 80(4): 1291-335.
[12] Stephane M, Alexandra C, Isabelle P, [J]. Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC gammal: implication in stem cell factor radioprotective effect [J]. Blood,2002, 100(4): 1294-301.
[13] Mai HQ, May WS, Gao FQ, et al. A functional role for nicotine inBcl2 phosphorylation and suppression of apoptosis [J]. J Biol Chem, 2003, 278(3): 1886-91.