Establishing a paclitaxel-resistant BNX mouse model of human lung cancer / 第二军医大学学报

ABSTRACT

Objective To establish a paclitaxel-resistant BNX mouse model of human lung carcinoma, so as to provide evidences for studying chemoresistant mechanism and for screening of the reversal drugs in vivo. Methods The resistant model was produced by repeating a crossover subcutaneous injection of human lung cancer A549-Taxol cells and transplantation of tumor fragment into immune deficiency mice, so as to increase the tumor forming rate of A549-Taxol cells and shorten the tumor forming time. The expressions of GST-k, P-gpl70 and MMP-7 were examined by immunohistochemical staining. The chemosensitivities of tumor cells to Taxol were tested and IC50 was measured by MTT. Results Tumor niduses were observed subcutaneously in SCID mice 4 months after injection of A549-Taxol cells, and then the tumor fragment or the tumor cells suspension were injected to SCID mice again. After 3 times of crossover injection, the tumor cells grew faster and tumor niduses were formed 2 months after injection. The same procedure was done in BNX mice. Finally, we achieved a successful rate of 80% in tumor implantation in BNX mice; the tumor niduses could be formed in 3 weeks. P-gpl70, GST-* and MMP-7 expression was higher in the experiment group than that in the A549 control group. IC50 value of paclitaxel for A549-Taxol cells was 520 folds that of A549 cells. Conclusion We have successfully established paclitaxel-resistant lung carcinoma model in mice, which provides a new platform for further study on chemoresistant reversal strategy and individualized clinical treatment.