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

IF 3.8 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Journal of Functional Foods Pub Date : 2024-09-23 DOI:10.1016/j.jff.2024.106463

Yujia Liu , Qing Li , Luo Fang , Xiaoping Hu , Zongfu Pan , Qing Hu , Mengting Cheng , Xinyu Tao , Yiwen Zhang , Ping Huang

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Abstract

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.

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拉帕尼精子通过 ATG9A 介导的自噬作用重塑肿瘤基质并增强奥沙利铂在结直肠癌中的抗肿瘤效果

奥沙利铂是治疗结直肠癌的一线化疗药物。然而，肿瘤基质中致密的胶原蛋白网络大大降低了奥沙利铂的渗透性和疗效。因此，迫切需要研究进一步提高 CRC 细胞对奥沙利铂敏感性的策略。在这项研究中，我们发现拉帕尼精子与奥沙利铂具有很强的协同作用，通过重塑肿瘤基质和破坏胶原蛋白来抑制 CRC 肿瘤的生长。进一步的研究发现，ATG9A 介导的自噬对于拉帕替尼诱导的胶原降解至关重要，这一过程可能是由自噬降解胶原转录因子 STAT3 介导的。综上所述，我们的研究首次评估了思密达和奥沙利铂在 CRC 中的协同作用，并评估了重塑基质作为未来化疗增敏的一种有前途的方法的新机遇。

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.