B7-H3 increases the radioresistance of gastric cancer cells through regulating baseline levels of cell autophagy.

Gastric cancer remains the second leading cause of cancer-related deaths worldwide. Adjuvant therapy has been shown to improve survival and is delivered either postoperatively (chemoradiotherapy) or perioperatively (chemotherapy) in Western countries. Debate continues regarding which of these approaches is an optimal strategy. Radioresistance in gastric cancer cells remains a serious concern. B7 homologue 3 (B7-H3, CD276), a newly found member of B7 immunoregulatory family, was found to be expressed in aberrant gastric cancer cells, and played a direct role in gastric cancer progression systems in a previous study. With upregulation or downregulation of B7-H3, it was observed that B7-H3 could increase radiotherapy resistance of gastric cancer cells by modulating apoptosis, cell cycle progression, and DNA double-strand breaks. Furthermore, it was found that B7-H3 could regulate baseline levels of cell autophagy. B7-H3 expression was negatively correlated with LC3-B expression in gastric cancer tissues. It was found that increasing baseline levels of cell autophagy with rapamycin in B7-H3-overexpressing cells could improve their sensitivity to radiation. This protein also exerted its function by modulating apoptosis and DNA double-strand breaks. Overall, it is demonstrated that B7-H3 increases the radiotherapy resistance of gastric cancer cells through regulating baseline levels of cell autophagy.