【Animal Modeling】-Establishment and identification of paclitaxel-resistant lung orthotopic mouse xenograft model

  Objective To establish an animal model of lung orthotopic transplantation of paclitaxel-resistant tumor and study the drug resistance mechanism.

  Methods Paclitaxel-resistant lung cancer cell line (A549-Taxol) obtained in our laboratory was used to determine its drug resistance index and cell sensitivity to anticancer drugs. About 5 × 106 cells per ml were injected into mice by puncture method. In the lungs, the survival rate and tumor formation rate were counted after 3 weeks, and the status of the mice was observed. RT-PCR and Western Blot techniques were used to detect the mRNA and protein expressions of drug resistance genes GST-π, P-gp170 and MMP-7 in tumors.

  Results The drug resistance index of A549-Taxol lung cancer cells was 508 times; the expression of GST-π, P-gp170 and MMP-7 drug resistance proteins were significantly increased (P < 0.001), and the invasive ability of lung cancer cells in A549-Taxol group was significantly increased. significantly higher than the A549 group. The survival rate and tumor formation rate were 100% and 85%, respectively, when 5 × 106 cells were injected into the lungs with a 5 mm needle. Immunohistochemistry showed that the drug resistance protein was significantly expressed in the nude mice of the A549-Taxol group. , and the drug resistance protein was higher than that of A549 nude mice group.

  Conclusion The expressions of GST-π, P-gp170 and MMP-7 are related to the resistance of lung cancer to paclitaxel. A paclitaxel-resistant orthotopic animal model of lung cancer was preliminarily established. The resistance of drug-resistant cells to paclitaxel remained stable and could be used in subsequent experiments. Research.