Objective To explore the mechanism of oridonin in inhibiting proliferation of gastric cancer cells and enhancing chemosensitivity of cetuximab.
Methods The SGC7901 gastric cancer cell lines were treated with different concentrations of oridonin or the same concentration of oridonin at different time points, and the proliferation levels were detected by MTT. After oridonin, cetuximab, oridonin combined with cetuximab were co-cultured with SGC7901 gastric cancer cell lines, the flow cytometry was used to detect the apoptosis rate and cell cycle. Western blot was used to detect the phosphorylation of epidermal growth factor receptor (EGFR), protein kinase B (Akt), extracellular regulatory protein kinase (ERK), signal transduction and activator of transcription 3 (STAT3) in cells, and real-time PCR was used to detect the transcriptional level of Bcl-xL and Cyclin D1.
Results Oridonin had a time and concentration dependent effect on the proliferation of SGC7901 gastric cancer cell lines. The higher the concentration was, the lower the proliferation level was. The inhibitory effects of oridonin at the same concentration on cell proliferation increased with time, and there was significant difference (P<0.05). The results of apoptosis detected by flow cytometry showed that the mortality of SGC7901 gastric cancer cell line was (2.90±0.90)% without drug intervention, and cetuximab was (9.30±2.20)%, the apoptosis rate of oridonin was (18.20±4.20)%, and the apoptosis rate of oridonin combined with cetuximab was (57.10±8.70)%, which were significantly higher than that of other groups (P<0.05).The expression levels of pEGFR, pAKT, pERK and pSTAT3 decreased in SGC7901 gastric cancer cells treated with oridonin and cetuximab, Bcl-xL and Cyclin D1 mRNA transcription decreased, and there were significant differences when compared with oridonin group and cetuximab group (P<0.05).
Conclusion Oridonin inhibits proliferation of gastric cancer cells and enhances chemosensitivity of cetuximab by inhibiting EGFR/STAT3 pathway.
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