Synergistic effect of morin and paclitaxel impedes cell proliferation through PI3K/AKT/STAT3 signaling axis inhibition in gastric cancer.

Gastric cancer (GC) is one of the most prevalent malignant cancers, with currently unsuccessful treatment strategies for patients. Increased PI3K/AKT/STAT-3 pathway activity has been observed in patients with GC. Morin (MRN), which is a flavonoid, exhibits significant anticancer activity by inhibiting the PI3K/AKT signaling pathway. However, monotherapy with MRN has faced challenges due to poor bioavailability and rapid elimination. This study investigated the combined effects of MRN and paclitaxel (PTX) on apoptosis induction and their molecular mechanisms in GC cells (HGT-1). After 24 h of MRN and PTX exposure, various assays were performed to assess the suppression of HGT-1 cell proliferation. These included cytotoxicity assessments, reactive oxygen species (ROS) level measurements, apoptotic morphological features, mitochondrial membrane potential (ΔΨm), nuclear fragmentation, and cell cycle analysis. Further, the effect of MRN and PTX on STAT-3 expression and various proliferation and apoptotic proteins was investigated using western blotting. The results revealed that the MRN and PTX combination significantly induced cytotoxicity, increased ROS levels, and altered ΔΨm, resulting in HGT-1 cell apoptosis (P<0.05). Furthermore, MRN and PTX treatment decreased the expression of oncogenic proteins, such as C-Fos, KRAS, and p-ERK1, in HGT-1 cells (P<0.05). The combination treatment inhibited PI3K, AKT, and STAT3 expressions, thereby suppressing proliferation and inducing proapoptotic protein expression in HGT-1 cells. Therefore, the combination of MRN and PTX could serve as a therapeutic approach for malignant GC treatment.