Effect of Chinese medicine prescriptions of warming-Yang or cooling-heat combined with Gefitinib on H1650 cell line

Purpose: The warming-Yang or cooling-heat is the principle rules of traditional Chinese medicine theory. The purpose of this study is to identify the effect of warming-Yang or cooling-heat Chinese medicine prescriptions combining with Gefitinib on lung cancer H1650 cell line. Materials and Methods: The typical warming-Yang prescription, Shen-fu (SF) Injection, and cooling-heat prescription, Qing-kai-ling (QKL) Injection was combined with Gefitinib respectively to treat H1650 cells. Cell viability was measured by MTT assay and Annexin V/PI method. Epidermal growth factor receptor (EGFR) pathway proteins were detected by Western blot. Results: QKL combined with Gefitinib significantly suppressed cell proliferation and induced apoptosis in H1650 cell line compared with single drug (P < 0.05). On the contrary, SF and Gefitinib had significant antagonism effects on both cell viability inhibition and apoptosis (48h：0.85 < Q < 1.15, 72h：Q < 0.85). Although higher EGFR protein level was observed in Gefitinib group, which was significantly reduced in QKL + Gefitinib group, no significant differences were observed in the levels of p-EGFR (P > 0.05), downstream AKT/p-AKT (P > 0.05), or ERK/p-ERK (P > 0.05) among Gefitinib, Gefitinib + SF, and Gefitinib + QKL groups. Conclusion: QKL Injection may reduce the level of EGFR and then improve the resistance of H1650 cells to EGFR-TKIs, which may be the mechanism of synergism effect of QKL Injection and Gefitinib. The principle rules of warming-Yang or cooling-heat should be further elucidated, and more research are required to explore the combined effect of Chinese medicine with opposite principle and Gefitinib