Synergistic effects of CP-25 and 5-fluorouracil on the hepatocellular carcinoma in vivo and in vitro through regulating activating mitochondrial pathway

Chang, Wei; Jiang, Xiao-Pei; Jin, Shuai; Li, Pei-Pei; Song, Sha-Sha; Yuan, Ping-Fan; Wei, Wei; Lu, Jing-Tao

doi:10.7150/jca.54702

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J Cancer 2022; 13(3):1005-1018. doi:10.7150/jca.54702 This issue Cite

Research Paper

Synergistic effects of CP-25 and 5-fluorouracil on the hepatocellular carcinoma in vivo and in vitro through regulating activating mitochondrial pathway

Wei Chang^#, Xiao-Pei Jiang^#, Shuai Jin, Pei-Pei Li, Sha-Sha Song, Ping-Fan Yuan, Wei Wei^✉, Jing-Tao Lu^✉

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, Anhui Province, China
^#These authors contributed equally to this work as co-first authors

Citation:

Chang W, Jiang XP, Jin S, Li PP, Song SS, Yuan PF, Wei W, Lu JT. Synergistic effects of CP-25 and 5-fluorouracil on the hepatocellular carcinoma in vivo and in vitro through regulating activating mitochondrial pathway. J Cancer 2022; 13(3):1005-1018. doi:10.7150/jca.54702. https://www.jcancer.org/v13p1005.htm

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Abstract

Paeoniflorin-6'-O-benzene sulfonate (CP-25) has therapeutic potential for the treatment of hepatocellular carcinoma (HCC). 5-Fluorouracil (5-Fu) has been a conventional chemotherapeutic agent for HCC. Unfortunately, the nonspecific cytotoxicity and multidrug resistance caused by long-term use limited the clinical efficacy of 5-Fu. This study was aimed to investigate whether the combination of CP-25 and 5-Fu could generate synergistic effect in inhibiting HCC. The experiments on the diethylnitrosamine (DEN) -induced mice showed that compared with applying single drugs, the combination of CP-25 and 5-Fu presented stronger inhibition in tumor nodule and volume. Meanwhile, CP-25 and 5-Fu activated the intrinsic mitochondrial apoptosis pathway induced by P53, inhibited anti-apoptotic B-cell lymphoma (Bcl-2), induced the pro-apoptotic Bcl-2-associated X protein (Bax), Cytochrome-C and caspases. In addition, the synergistic effect was also validated in Bel-7402 and HepG-2 cells in vitro. This research not only provides a novel and effective combination strategy for the therapy of HCC but also provides an experimental basis for the development of CP-25 and 5-Fu compound preparation.

Keywords: CP-25, Hepatocellular carcinoma, Diethylnitrosamine, Apoptosis, C57BL/6J

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APA

Chang, W., Jiang, X.P., Jin, S., Li, P.P., Song, S.S., Yuan, P.F., Wei, W., Lu, J.T. (2022). Synergistic effects of CP-25 and 5-fluorouracil on the hepatocellular carcinoma in vivo and in vitro through regulating activating mitochondrial pathway. Journal of Cancer, 13(3), 1005-1018. https://doi.org/10.7150/jca.54702.

ACS

Chang, W.; Jiang, X.P.; Jin, S.; Li, P.P.; Song, S.S.; Yuan, P.F.; Wei, W.; Lu, J.T. Synergistic effects of CP-25 and 5-fluorouracil on the hepatocellular carcinoma in vivo and in vitro through regulating activating mitochondrial pathway. J. Cancer 2022, 13 (3), 1005-1018. DOI: 10.7150/jca.54702.

NLM

CSE

Chang W, Jiang XP, Jin S, Li PP, Song SS, Yuan PF, Wei W, Lu JT. 2022. Synergistic effects of CP-25 and 5-fluorouracil on the hepatocellular carcinoma in vivo and in vitro through regulating activating mitochondrial pathway. J Cancer. 13(3):1005-1018.

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