Jichu yixue yu linchuang (Nov 2023)

Pachymic acid inhibits proliferation of human colon cancer cell line HT-29

  • FENG Naxin, WANG Peng, HE Mingxuan, LIU Jinyan

DOI
https://doi.org/10.16352/j.issn.1001-6325.2023.11.1673
Journal volume & issue
Vol. 43, no. 11
pp. 1673 – 1679

Abstract

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Objective To investigate the impacts of pachymic acid (PA) on proliferation and apoptosis of human colon cancer cell line (HT-29) and its potential mechanism. Methods The cells were divided into blank group, 20, 40 and 80 μmol/L PA groups. The proliferation of HT-29 cells was detected by MTT method; The cell cycle and apoptosis of HT-29 cells were detected by flow cytometry; The expression of cell cycle, apoptosis and Akt/MDM2/p53 signal pathway related proteins in HT-29 cells were detected by Western blot. The tumor xeno-transplantation model with HT-29 cells was constructed, and then the tumorigenic nude mice were randomly divided into control group, intra-peritoneal injection of 10, 30 and 60 mg/kg PA groups(6 in each group), the tumor volume and weight were measured; The expression of Ki-67 and of cleared caspase-3 proteins in tumor tissue was detected by immuno-histochemistry; The expression of Akt/MDM2/p53 signal pathway related protein in tumor tissue was detected by Western blot. Results PA of all doses obviously inhibited proliferation of HT-29 cells, the proportion of cells in S phase and in G2/M phase was deceased and the expression of B cell lymphoma gene-2(Bcl-2), cyclin D1, cycle protein dependent activating enzyme 2(CDK2) proteins all decreased, The ratios of p-Akt/Akt and p-MDM2/MDM2 in a concentration-dependent manner increased(P＜0.05).The apoptosis rate, the ratio of cells in G0/G1 phase and the protein expression of Bax, cleaved caspase-3 and p53 also increased(P＜0.05). PA in all dose groups obviously reduced the tumor volume, weight, the expression of Ki-67 protein and the ratios of p-Akt/Akt, p-MDM2/MDM2 in tumor tissue of nude mice (P＜0.05), and increased the protein expression of cleaved caspase-3 and p53 in tumor tissue(P＜0.05). Conclusions PA can induce apoptosis and cell cycle arrest of colon cancer cells and inhibit cell proliferation. Its mechanism may be related to the regulation of Akt/MDM2/p53 signal pathway.

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