Study on Reversal Effects of Levoshikonin on Cisplatin Resistance of Human Cervical Carcinoma HeLa Cells
- VernacularTitle:左旋紫草素对顺铂耐药人宫颈癌HeLa细胞的逆转作用研究
- Author:
Chunshuang DU
1
;
Yani MA
2
;
Shuai WANG
2
;
Fei ZHANG
1
;
Jie ZHANG
1
;
Guangjian SANG
1
Author Information
1. Dept. of Pharmacy，Tianjin Medical University Cancer Institute ＆Hospital/National Clinical Research Center for Cancer/ Tianjin Key Laboratory of Cancer Prevention and Therapy/Tianjin’s Clinical Research Center for Cancer，Tianjin 300060，China
2. College of Pharmacy，Tianjin Medical University，Tianjin 300041，China
- Publication Type:Journal Article
- Keywords:
Human cervical carcinoma HeLa cells;
Levoshikonin;
Cisplatin;
Resistance;
Apoptosis;
Cell cycle;
Apoptosis-
- From:
China Pharmacy
2020;31(15):1867-1873
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To investigate the reversal effects and potential mechanism of levoshikonin （L-SHK）on cisplatin （DDP）resistance of human cervical carcinoma HeLa cells. METHODS ：Human cervical carcinoma HeLa cells were used as research objects ，and drug-resistant HeLa/DDP cells were induced by DDP. CCK- 8 assay was used to determine drug resistance index of HeLa/DDP cells ，the inhibition rate of different doses of L-SHK （0.125，0.25，0.5，1，2，4，8，16 μmol/L）on cell proliferation，IC50 and the reversion index of L-SHK on HeLa/DDP cells. Effects of low ，medium and high doses of L-SHK （0.3， 0.6，1.2 μmol/L）combined with DDP on cell cycle and apoptosis rate were determined by flow cytometry. Western blotting assay was used to detect the effects of low ，medium and high doses of L-SHK （0.3，0.6，1.2 μmol/L）combined with DDP on the expression of apoptosis-related protein （Cleaved caspase- 3，Bcl-2 and Bax ）. RESULTS ：The drug resistance index of HeLa/DDP cells was 11.8. The inhibition rate of L-SHK on HeLa/DDP cells increased with the increase of dose. Compared with DDP alone ， IC50 of DDP+low-dose ，medium-dose and high-dose L-SHK groups were decreased significantly ，with a dose-dependent manner （P＜0.05）. The reversion indexes were 1.38，2.80，6.71 in DDP+low-dose ，medium-dose and high-dose L-SHK groups. Compared with blank control group ，the proportion of cells at phase G 0/G1 and phase S in administration groups ，as well as early and late apoptosis rate and total apoptosis rate of cells ，the protein expression of Bax and Cleaved caspase- 3 in L-SHK combination groups were increased significantly ；the proportion of cells at phase G 2/M in administration group as well as the protein expression of Bcl-2 in L-SHK combination groups were decreased significantly （P＜0.05）. Compared with DDP group ，the proportion of cells at phase S and G 2/M and the protein expression of Bcl- 2 in L-SHK combination groups were significantly decreased ；the proportion of cells at phase G 0/G1，early and late apoptosis rate and total apoptosis rate ，the protein expression of Bax and Cleaved caspase- 3 in L-SHK combination groups were significantly increased （P＜0.05）. CONCLUSIONS ：HeLa/DDP cells are resistant to DDP ，and L-SHK can reverse the drug resistance. L-SHK combined with DDP can promote the apoptosis of HeLa/DDP cells ，which is better than DDP alone. Its mechanism may be related to the influence of cell cycle and the regulation of apoptosis-related protein expression.
