BVAN08 enhances radiosensitivity via downregulation of DNA-PKcs towards hepatic tumor xenograft

Abstract

Objective: To study the effects of the novel vanillin derivative BVAN08 on the radiosensitivity of hepatic cancer cells for the purpose of providing evidence for its potential use as a potential radiosensitive drug. Methods: Hepatic cancer Huh-7 ​cells labeled with luciferase were used to investigate the radiosensitivity induced by BVAN08 in vivo. Colony formation assays and flow cytometry were used to measure the apoptosis and radiosensitivity of Huh-7 ​cells in vitro produced by BVAN08. Histology and immunohistochemistry were used to evaluate the toxicity of BVAN08 in vivo. Results: BVAN08 induced apoptosis and cell cycle arrest of Huh-7 ​cells in a time-dependent manner. Moreover, BVAN08 combined with radiation increased the sensitivity of Huh-7 ​cells to γ-ray radiation and significantly inhibited tumor growth in vivo. The tumor inhibition rates of the BVAN08 treatment group, irradiation treatment group, and combined therapy group were 58%, 38%, and 85%, respectively. The DNA-PKcs expression in tumor tissues of the BVAN08 treatment group was lower than that of the control group (P ​< ​0.01). BVAN08 inhibited the growth of Huh-7 ​cells in nude mice bearing tumors, without resulting in any noticeable side effects on bodyweight, livers, hearts, kidneys, or the number of peripheral white blood cells. Conclusions: As a natural food additive derivative, BVAN08 possesses the potential to be used as an effective anti-cancer drug to increase cell sensitivity to radiotherapy.

Keywords

• Vanillin derivative
• Cell cycle
• Apoptosis
• DNA-PKcs
• Radiosensitivity