Cisplatin inhibites HeLa cell proliferation by suppressing activation of metastasis suppressor gene 1-extracellular signal-regulated kinase/serine-threonine kinase
10.3867/j.issn.1000-3002.2016.04.008
- VernacularTitle:顺铂通过抑制转移抑制基因1-细胞外信号调节激酶及丝氨酸/苏氨酸激酶激活抑制HeLa细胞增殖
- Author:
Si ZHANG
;
Yuanlin LIU
;
Xue LI
;
Xiangdong ZHOU
;
Yue ZHAO
;
Pingping ZHANG
;
Ying TONG
;
Yi ZHANG
- Publication Type:Journal Article
- Keywords:
cisplatin;
HeLa cells;
extracellular signal-regulated kinase;
serine-threonine kinase;
metastasis suppressor gene 1
- From:
Chinese Journal of Pharmacology and Toxicology
2016;30(4):350-355
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the molecular mechanism of cisplatin(DDP)by which HeLa cell growth and proliferation are inhibited. METHODS Cultured HeLa cells were treated with DDP 0.02-75 μmol · L-1 for 24 or 48 h. CCK-8 assay was used to determine the cell proliferation. The wound scratch assay was used to detect the cell migration and invasion. Flow cytometry was used to detect the cell cycle arresting. q-PCR was used to test the expression of metastasis suppressor gene 1 (MTSS1)mRNA. Western blot was used to determine protein levels of MTSS1,phosphorylated-extra?cellular signal-regulated kinase(p-ERK) and phosphorylated-serine-threonine kinase(p-AKT). RESULTS Following the treatment with DDP for 24 or 48 h,the proliferation of HeLa cells was inhibited significantly (P<0.05),the value of the half inhibitory concentration (IC50) of cells was 4.14 and 11.82 μmol · L-1. Migration and invasion activity of HeLa cells were reduced according to the wound scratch assay(P<0.05). Flow cytometry results showed that the cell cycle was arrested at S phase. q-PCR results showed that MTSS1 mRNA expression changed with DDP in a concentration-dependent manner (r24 h=-0.965,P<0.01;r48 h=-0.953,P<0.01). Western blot showed that the protein levels of MTSS1,p-ERK and p-AKT expression declined significantly with the increase in DDP concentrations(p-ERK:r24 h=-0.875,P<0.01;r48 h=-0.966,P<0.01. p-AKT:r24 h=-0.831,P<0.01;r48 h=-0.863,P<0.01. MTSS1:r24 h=-0.969,P<0.01;r48 h=-0.988,P<0.01). CONCLUSION DDP treatment inhibits HeLa growth and proliferation by interfering with the MTSS1 expression and disturbing the activation of ERK and AKT signaling pathways.
