Objective: To study the effect of aqueous extract of Taxus chinensis var. mairei (AETC) combined Erlotnib on the growth of A549 xenograft in nude mice and its mechanism.
Methods: The xenograft model in nude mice was established by inoculating A549 cells subcutaneously. BALB/c nude mice bearing A549 xenograft were randomly divided into six groups, i.e., the low dose Erlotinib group (A) , the standard dose Erlotnib group (B) , the low dose Erlotinib combined AETC group (C), the standard dose Erlotnib combined AETC group (D), the AETC group (E), the control group (F), 12 in each group. Different medication was performed for 7 successive weeks after 24 h. One mL blood was withdrawn and tumor tissues taken. The tumor inhibition rate was calculated. The combined effect was analyzed by Jin's Formula [Q = Ea + b/(Ea + Eb-Ea x Eb) ]. mRNA and protein expression levels of epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), and B cell lymphoma-2 (Bcl-2) in xenografts were detected using real-time RT-PCR and ELISA.
Results: Compared with Group F, the xenograft weight was obviously lowered in Group B-E (P < 0.05, P < 0.01). The q value was 0.92 in Group C and 0.96 in Group D, which was obtained by simple adding of the two drugs. Compared with Group F, EG- FR mRNA expression in Group D and E, COX-2 mRNA expression in Group A-E; Bcl-2 mRNA expression in Group B-D; COX-2 protein expression in Group B-E; Bcl-2 protein expression in Group C and D were obviously lowered with statistical difference (P < 0.05, P < 0.01).
Conclusions: AETC combined low dose and standard dose Erlotinib had synergistic effect on tumor inhibition. Its mechanism might be associated with down-regulating mRNA and protein expression levels of COX-2 and Bcl-2.