Synergistic effect of combining paeonol and cisplatin on apoptotic induction of human hepatoma cell lines

Authors: XU, Shu-ping¹; SUN, Guo-ping; SHEN, Yu-xian¹; PENG, Wan-ren²; WANG, Hua³; WEI, Wei¹

Source: Acta Pharmacologica Sinica, Volume 28, Number 6, June 2007 , pp. 869-878(10)

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Abstract:

Aim: 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. Conclusion: 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.

Keywords: paeonol; cisplatin; drug interaction; human hepatoma cell line; apoptosis; cell cycle

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2007.00564.x

Affiliations: 1: 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 2: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China 3: Department of Oncology, Provincial Hospital of Anhui, Hefei 230001, China

Publication date: 2007-06-01

Synergistic effect of combining paeonol and cisplatin on apoptotic induction of human hepatoma cell lines

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