Synergistic effect of combining paeonol and cisplatin on apoptotic induction of human hepatoma cell lines.
OBJECTIVE
To investigate whether paeonol (Pae) has synergistic effects with cisplatin (CDDP) on the growth-inhibition and apoptosis-induction of human hepatoma cell lines HepG2 and SMMC-7721.


METHODS
The cytotoxic effect of drugs was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The coefficient of drug interaction was used to analyze the nature of drug interactions. Morphological changes were observed by acridine orange fluorescence staining. Cell cycle and the apoptosis rate were detected by flow cytometry. Bcl-2 and Bax expression were assayed by immunohistochemical staining.


RESULTS
Pae or CDDP had antiproliferative effect on the 2 cell lines in a dose-dependent manner, with different sensitivities to drugs. More interestingly, a synergistic inhibitory effect on the viability of the 2 cell lines was observed after treatment with a combination of Pae (15.63, 31.25, and 62.5 mg/L) with various concentrations of CDDP. Further study showed typical morphological changes of apoptosis if the cells were exposed to the two agents for 24 h. The apoptotic rate of the cells with combination treatment was significantly higher than that of cells treated with Pae or CDDP alone. The expression of Bcl-2 decreased and that of Bax increased in the treated groups, especially in the combination group, with the ratio of Bcl-2/Bax decreasing correspondingly. Additionally, a combination of Pae with CDDP resulted in a stronger S phase arrest, compared with Pae or CDDP alone.


CONCLUSIONS
Pae, in combination with CDDP, had a significantly synergistic growth-inhibitory and apoptosis-inducing effect on the 2 human hepatoma cell lines, which may be useful in hepatoma treatment.
Xu
Shu-Ping
SP
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunological Pharmacology, Key Laboratory of Research and Development of Chinese Medicine, Hefei 230032, China. sunguoping@ahmu.edu.cn
Sun
Guo-Ping
GP
Shen
Yu-Xian
YX
Peng
Wan-Ren
WR
Wang
Hua
H
Wei
Wei
W
D000098:Acetophenones / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000098:Acetophenones; D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C013638:paeonol; D002945:Cisplatin