Objective To establish an animal model of paclitaxel resistant tumor after orthotopic lung transplantation and study the mechanism of drug resistance.
Methods The 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, and then the drug resistance index and cell sensitivity to anticancer drugs were measured × 106 cells were injected into the lungs of mice. After 3 weeks, the survival rate and tumor formation rate were counted and the status of mice was observed. RT-PCR and Western Blot were used to detect the mRNA and protein expression 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 resistance protein increased significantly (P<0.001), and the invasive ability of lung cancer cells in A549 Taxol group was significantly higher than that in A549 group. Use 5 × The survival rate and tumorigenicity rate of 106 cells injected into the lungs with a volume of 5 mm were 100% and 85% respectively. Immunohistochemistry after tumorigenesis showed that the drug resistant protein was significantly expressed in A549 Taxol group nude mice, and the drug resistant protein was higher than that in A549 nude mice group.
Conclusion The expression of GST - π, P-gp170 and MMP-7 is related to paclitaxel resistance in lung cancer. An in situ animal model of paclitaxel resistant lung cancer has been preliminarily established. The drug resistance of drug resistant cells to paclitaxel remains stable and can be used for subsequent experimental studies.