Combined effect of recombinant human adenovirus p53 and curcumin in the treatment of liver cancer

Abstract

The development of an effective therapeutic intervention for liver cancer is a worldwide challenge that remains to be adequately addressed. Of note, TP53, which encodes the p53 protein, is an important tumor suppressor gene, 61% of TP53 is functionally inactivated in liver cancer. Recombinant human adenovirus p53 (rAd-p53) is the first commercial product that has been used for gene therapy. In the present study, the combined mechanistic effects of rAd-p53 and curcumin, a naturally occurring compound with previously reported anti-inflammatory, antioxidant and anti-cancer properties, were assessed in liver cancer cells, using HepG2 cells as the model cell line. The administration of either curcumin or rAd-p53 promoted apoptosis, suppressed epithelial-mesenchymal transition (EMT) and blocked G2/M phase progression in HepG2 cells, which were potentiated further when both agents were applied together. Combined rAd-p53 and curcumin treatment resulted in higher p53 (P<0.01) and p21 (P<0.01) expression compared with rAd-p53 or curcumin were added alone, suggesting an additive effect on TP53 expression. Additionally, curcumin and rAd-p53 were demonstrated to regulate the activation of mitogen-activated protein kinases (MAPKs) ERK1/2, p38 MAPK and JNK. These results indicated that the combination of rAd-p53 with curcumin synergistically potentiates apoptosis and inhibit EMT compared with either rAd-p53 or curcumin treatment alone via the regulation of TP53 regulation. Mechanistically, this effect on TP53 expression may involve the ERK1/2, p38 MAPK and JNK signaling pathways. The current study provides new insights that can potentially advance the development of therapeutic strategies for liver cancer treatment.

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