Zeng Hui, Li Hu, Wang Li, You Shuang, Liu Shuaibin, Dong Xiaojing, He Fan, Dai Jingcong, Wei Quan, Dong Zhiyong, Zhang Yanli, Yang Jingbo, Yang Xia, Wang Jian, Hu Lina
Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Joint International Research Lab for Reproduction and Development, Ministry of Education, Chongqing 400010, China.
Mater Today Bio. 2024 Sep 1;28:101220. doi: 10.1016/j.mtbio.2024.101220. eCollection 2024 Oct.
Ovarian cancer (OC) is one of the leading causes of death from malignancy in women and lacks safe and efficient treatment. The novel biomaterial, recombinant humanized collagen type III (rhCOLIII), has been reported to have various biological functions, but its role in OC is unclear. This study aimed to reveal the function and mechanism of action of rhCOLIII in OC. We developed an injectable recombinant human collagen (rhCOL)-derived material with a molecular weight of 45 kDa, with a stable triple helix structure, high biocompatibility, water solubility and biosafety. The anti-tumor activity of rhCOLIII was comprehensively evaluated through experiments. , our results showed that rhCOLIII inhibited the proliferation, migration, and invasion of ovarian cancer cells (OCCs), and induced apoptosis. In addition, rhCOLIII not only inhibited autophagy of OCCs but also increased the expression of MHC-1 molecule within OCCs. To further elucidate the mechanism of rhCOLIII in OC, we conducted joint analysis of RNA-Seq and proteomics, and found that rhCOLIII exerted anti-tumor function and autophagy inhibition by downregulating Glutathione S-transferase P1 (GSTP1). Furthermore, various rescue experiments were designed to demonstrate that rhCOLIII suppressed autophagy and proliferation of OCCs by mediating GSTP1. , we found that rhCOLIII could inhibit tumor growth and promote CD8 T cell infiltration. Our results indicate that rhCOLIII has great anti-tumor potential activity in OC, and induces protective anti-tumor immunity by regulating autophagy through GSTP1. These findings illustrate the potential therapeutic prospects of rhCOLIII for OC treatment.
卵巢癌（OC）是女性恶性肿瘤死亡的主要原因之一，且缺乏安全有效的治疗方法。据报道，新型生物材料重组人III型胶原蛋白（rhCOLIII）具有多种生物学功能，但其在卵巢癌中的作用尚不清楚。本研究旨在揭示rhCOLIII在卵巢癌中的功能及作用机制。我们研发了一种分子量为45 kDa的可注射重组人胶原蛋白（rhCOL）衍生材料，其具有稳定的三螺旋结构、高生物相容性、水溶性和生物安全性。通过实验全面评估了rhCOLIII的抗肿瘤活性。结果表明，rhCOLIII抑制卵巢癌细胞（OCCs）的增殖、迁移和侵袭，并诱导细胞凋亡。此外，rhCOLIII不仅抑制OCCs的自噬，还增加了OCCs内MHC-1分子的表达。为进一步阐明rhCOLIII在卵巢癌中的作用机制，我们对RNA测序和蛋白质组学进行了联合分析，发现rhCOLIII通过下调谷胱甘肽S-转移酶P1（GSTP1）发挥抗肿瘤功能并抑制自噬。此外，设计了各种挽救实验以证明rhCOLIII通过介导GSTP1抑制OCCs的自噬和增殖。我们发现rhCOLIII可以抑制肿瘤生长并促进CD8 T细胞浸润。我们的结果表明，rhCOLIII在卵巢癌中具有巨大的抗肿瘤潜在活性，并通过GSTP1调节自噬诱导保护性抗肿瘤免疫。这些发现阐明了rhCOLIII在卵巢癌治疗中的潜在治疗前景。
