JI-CJ001 Enhances Paclitaxel Sensitivity in Gastric Cancer Cell Lines through Inhibition of HER2/mTOR Signaling and Induction of Autophagy

Background/Aim: Addressing chemoresistance remains a significant challenge in cancer therapy. Human epidermal growth factor receptor 2 (HER2) signaling and autophagy are central mechanisms contributing to drug resistance by mitigating drug-induced cytotoxic stress and supporting cancer cell survival. Although JI-CJ001 has shown anticancer activity in several cancer models, the effects of JI-CJ001 in combination with paclitaxel (PTX) in gastric cancer remain unclear. Materials and Methods: In this study, we examined whether JI-CJ001 modulates HER2 signaling and autophagy to potentiate the sensitivity of gastric cancer cells to PTX, a widely used chemotherapeutic agent. To do so, we employed cytotoxicity assays and mechanistic evaluations, including western blotting, flow cytometry, and confocal imaging, to analyze autophagy-related pathways in gastric cancer cell lines. Results: Our data show that co-treatment with JI-CJ001 and PTX suppressed cell growth by reducing HER2/mTOR signaling and promoting LC3 and p62 accumulation. The combination initiates autophagy by downregulating STAT3 and disrupting interaction between Mcl-1 and Beclin1. In a gastric cancer xenograft model, JI-CJ001 plus PTX produced significant anti-tumor effects. Conclusion: Collectively, these findings indicate that JI-CJ001 enhances the therapeutic impact of PTX in gastric cancer cell lines through regulation of HER2/mTOR signaling and autophagy. These results highlight JI-CJ001 as a promising natural adjuvant for improving the efficacy of conventional chemotherapy in gastric cancer.