ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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 Different medication was performed for 7 successive weeks after 24 h. One mL blood was withdrawn and tumor tissues taken.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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Animals , Mice , Antineoplastic Agents , Pharmacology , Antineoplastic Combined Chemotherapy Protocols , Pharmacology , Cell Line, Tumor , Cyclooxygenase 2 , Metabolism , Drugs, Chinese Herbal , Pharmacology , Enzyme Inhibitors , Pharmacology , Erlotinib Hydrochloride , Pharmacology , Heterografts , Lung Neoplasms , Mice, Inbred BALB C , Mice, Nude , ErbB Receptors , Metabolism , Taxus , Transplantation, HeterologousABSTRACT
<p><b>OBJECTIVE</b>To study the effect of aqueous extract of Taxus chinensis var. mairei (AETC) on the growth of A549 lung cancer xenografts in nude mice and its mechanism.</p><p><b>METHOD</b>The A549 lung cancer xenograft model was established, and then randomly divided into the control group, and low, middle and high dose AETC experiment groups. After 24 hours, they were orally administered with normal saline and drugs of the same volume for seven weeks. The length and width of the xenografts were measured every three days, and the xenograft growth curve was drawn. The nude mice were sacrificed after the administration for seven weeks, and their xenografts were collected to cultivate the anti-tumor rate. Real-time PCR and Western-blot were adopted to detect mRNA and protein levels.</p><p><b>RESULT</b>All of AETC experiment groups showed a significant anti-tumor effect (P < 0.05). Compared with the control group, each experimental group showed notable reduction in EGFR and Survivin mRNA in xenograft tissues (P < 0.05), with no significant change in VEGF mRNA level. The analysis on gray value ratio showed that EGFR mRNA were down-regulated (P < 0.05) in xenograft tissues in all experimental groups, but with no statistical significance in difference, and Survivin and p-EGFR were significantly down-regulated.</p><p><b>CONCLUSION</b>AETC has not significant effect on angiogenesis, but may have the inhibitory effect on xenograft growth by inhibiting Survivin protein and EGFR phosphorylation.</p>