Autophagy induced synergistic inhibitory effect of cetuximab in combination with triptolide on proliferation and metastasis of colorectal SW480 cells / 中国药理学通报

ABSTRACT

Aim: To investigate the effect of triptolide combined with epidermal growth factor receptor monoclonal antibody cetuximab on the biological behavior of human colorectal cancer cell line SW480. Methods: MTT assay was used for estimating the survival rates of SW480 cells exposed to different concentrations and different durations of triptolid and cetuximab. Colony formation assay was used for showing the proliferation and wound healing assay was performed to assess the effects of drugs on cell migration, Western blot was used for testing the expression of LC3-II, p62, E-cadherin, Vimentin, mTOR, Snail, and Twist. Results: The SW480 growth of cells was inhibited by triptolide in a dose- and time-dependent manner and cetuximab was only in a dose-dependent manner. The combination regimen of cetuximab and triptolide exerted a synergistic effect. Triptolide could decrease expression of p62 increase expression of LC3-II and induce autophagic apoptosis. Triptolide monotherapy group and combination group could significantly inhibit EMT in SW480 cells, and the E-cadherin protein was up-regulated, Vimentin protein was down-regulated, and key molecules Snail and Twist were down-regulated. Conclusion: Triptolide combined with cetuximab has a synergistic effect on the inhibition of proliferation and metastasis of SW480 cells. Triptolide induces autophagic apoptosis by inhibiting the mTOR pathway. Autophagy mediated by triptolide can inhibit EMT of SW480 cells and may be a mechanism to reverse the resistance of cetuximab.