Semen Raphani Remodels tumor-stroma and Enhances the antitumor effect of Oxaliplatin via ATG9A mediated autophagy in colorectal cancer

• Raphani Semen could alleviate over-expression of intratumor collagen in CRC. • Raphani Semen could induce ATG9A mediated autophagy. • Semen Raphani activates autophagy of collagen transcription factor STAT3. • Raphani Semen could increase antitumor effect of Oxaliplatin of CRC. Colorectal cancer is one of the most common cancers and the main causes of mortality around the world and Oxaliplatin is a first-line chemotherapy agent for treatment of CRC. However, the dense collagen network in tumors stroma significantly reduces the penetration and efficacy of Oxaliplatin. Therefore, research strategies to further sensitize CRC cells to Oxaliplatin are urgently needed. In this study, we showed that Semen Raphani exhibited a strong synergy with Oxaliplatin to inhibit CRC tumor growth by remodeling tumor stroma and depredate collagen. Further research found that ATG9A mediated autophagy is critical for the collagen degradation induced by Semen Raphani , this process may be mediated by the degradation of collagen transcription factor STAT3 by autophagy. Taken together, our study is the first to evaluate the synergy of Semen Raphani and Oxaliplatin in CRC and to assess new opportunities for remodeling stroma as a promising approach for future chemotherapy sensitization.