Huashi Jiedu decoction blocks cell cycle and inhibits EMT of gastric cells via LncRNA-p21

Abstract

Background: MicroRNAs and traditional Chinese medicine have emerged as pivotal regulators in the progression of gastric carcinoma. Huashi Jiedu decoction has been clinically used to enhance the quality of life in gastric carcinoma patients. Therefore, the present study aimed to elucidate the involvement of MicroRNAs and Huashi Jiedu decoction in gastric carcinoma metastasis and investigate their regulatory mechanisms in anti-tumor effects. Methods: Subsequently, the effect of Huashi Jiedu decoction on gastric carcinoma cell metastasis and proliferation was verified using cell counting kit-8, flow cytometry, wounding healing, and Transwell assays. LncRNA-p21 knockdown cells were successfully established in BGC-823 and MGC-803 cell lines. Mouse models inoculated with MGC-803 cells were generated, and the cellular morphology in tissues was assessed using hematoxylin staining. Additionally, western blot and immunohistochemistry analysis were performed to evaluate the expression of epithelial-mesenchymal transition-related proteins, with real-time PCR validation conducted in both in vitro and in vivo settings. Results: Network pharmacology revealed a close association between proteins involved in the epithelial-mesenchymal transition process and LncRNA-p21 in gastric carcinoma, consistent with the downregulated expression of E-cadherin, N-cadherin, and Twist following LncRNA-p21 knockdown. Cell counting kit-8 and flow cytometry assays confirmed that Huashi Jiedu decoction exhibited concentration-dependent cytotoxicity, effectively inhibiting the distant metastasis of gastric carcinoma cells in wound healing and invasion experiments. Treatment with Huashi Jiedu decoction resulted in increased expression of E-cadherin, N-cadherin, and LncRNA-p21 in both in vitro and in vivo models, as validated by western blot, real-time PCR, and immunohistochemistry. Conclusion: Collectively, our findings demonstrate that Huashi Jiedu decoction suppresses epithelial-mesenchymal transition and inhibits gastric carcinoma invasion and metastasis both in vivo and in vitro through the knockdown of LncRNA-p21, corroborating the initial findings from our network pharmacology analysis.