Induction of Apoptosis, Inhibition of MCL-1, and VEGF-A Expression Are Associated with the Anti-Cancer Efficacy of Magnolol Combined with Regorafenib in Hepatocellular Carcinoma

Cancers

Fei-Ting Hsu¹  Jiann-Hwa Chen²  Wei-Lung Chen²  Cheng-Hsien Chen³ 

[1] Department of Biological Science and Technology, China Medical University, Taichung 406, Taiwan;Department of Emergency Medicine, Cathay General Hospital, Taipei 106, Taiwan;Surgical Department of Show Chwan Memorial Hospital, Changhua 500, Taiwan;

关键词: magnolol;    regorafenib;    apoptosis;    MCL-1;    VEGF-A;    hepatocellular carcinoma;   

DOI  :  10.3390/cancers13092066

来源: DOAJ

【 摘 要 】

While regorafenib was approved for the treatment of advanced HCC in 2017, with a partial response and survival benefit; other combination agents to facilitate the efficacy of regorafenib still need to be explored. Magnolol is a potential natural anti-tumor compound for many types of cancers. Combination indexes calculated on the basis of both in vitro and in vivo models have indicated a synergistic effect of the combination of regorafenib and magnolol. The overexpression of the VEGF-A protein significantly diminished regorafenib’s inhibition of cell viability, while the transient knockdown of VEGF-A by siRNA effectively sensitized HCC cells to regorafenib. In addition, the inhibition of MCL-1 by siRNA combined with regorafenib allowed for a significantly greater inhibition of cell growth, compared to regorafenib alone. A lower protein expression level for VEGF-A and MCL-1 was found for the combination treatment of HCC in vitro and in vivo. A superior metastasis inhibition was also found in the combination group, as compared to the single-treatment groups, using a transwell assay, wound healing assay, and Western blotting. The caspase-dependent and -independent and DNA damage effects, as determined by flow cytometry and a comet assay, were increased by the combination therapy. Taken together, magnolol sensitized HCC to regorafenib, which was correlated with the reduction of VEGF-A and MCL-1 and the induction of apoptosis.

【 授权许可】

Unknown