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.
ABSTRACT
OBJECTIVE:To analyze the characteristics and genernal patterns of adverse drug reactions(ADR)induced by antitumor drugs.METHODS:112 ADR cases induced by antitumor drugs included in CNKI from 2003 to 2007 were analyzed statistically in respect of patients' age and sex,primary diseases,drug categories,organs and systems involved and the clinical manifestations etc.RESULTS:Of the total 112 cases,patients aged from 51 to 60 years showed the highest incidence of ADR,accouting for 31.3%,and Platinum antitumor drugs showed the highest incidence of ADR,accounting for 36.6%.The most common presentation of ADR was lesion of nervers system(41.1%),followed by lesions of respirotory system(32.1%)and skin and the appendants(28.6%).CONCLUSION:Awareness on the reporting of ADR induced by antitumor drugs should be strengthened and the characteristics of the ADR should be analyzed to ensure clinical safe and rational use of antitumor drugs and avoid or reduce the incidence of ADR.