Erteng-Sanjie Capsule Enhances Chemosensitivity of 5-Fluorouracil in Tumor-Bearing Nude Mice with Gastric Cancer by Inhibiting Notch1/Hes1 Signaling Pathway.

Gastric cancer is one of the most common cancers worldwide. This study investigated the chemosensitivity-enhancing effects of Erteng-Sanjie capsule (ETSJC) in combination with 5-fluorouracil (5-FU) on gastric cancer and its possible underlying mechanisms. The study established a subcutaneous xenograft model of human gastric cancer. The animals were divided into five groups: the control group, the 5-FU group, the 5-FU + ETSJC low-dose group, the 5-FU + ETSJC medium-dose group, and the 5-FU + ETSJC high-dose group. The tumor volume and tumor weight were calculated. TUNEL staining was used to evaluate cell apoptosis. Immunohistochemical analysis was used to detect the expression of Ki67 cells and the CD31 microvessel density in tumors. Simultaneously, western blot analysis was applied to detect the expression of caspase-3, Bax, Bcl-2, Notch1, and Hes1 proteins. Compared with the control group, tumor volume and weight in the 5-FU and 5-FU + ETSJC groups were inhibited. Moreover, compared with the 5-FU group, tumor volume and weight were significantly inhibited in the 5-FU + ETSJC groups. The numbers of Ki67 cells, CD31 microvessel density, and the expression of Bcl-2, Notch1, and Hes1 proteins were markedly decreased in the combination group when compared with the chemotherapy alone group. The numbers of TUNEL cells and the expression of Bax and caspase-3 proteins were significantly increased in the 5-FU + ETSJC groups when compared with the 5-FU group. The therapeutic effects were demonstrated to be dose dependent. In conclusion, the findings of the study showed that ETSJC improved the chemosensitivity of 5-FU by blocking Notch1/Hes1 signaling pathway in gastric cancer-bearing mice.