【Animal Modeling】-Establishment and identification of paclitaxel-resistant lung transplanted tumor model in orthotopic mice

  OBJECTIVE: To establish an animal model of orthotopic lung transplantation for paclitaxel-resistant tumors and to study the mechanism of drug resistance.

  Method: Use the paclitaxel-resistant lung cancer cell line (A549-Taxol) obtained in our laboratory to measure the drug resistance index and cell sensitivity of anticancer drugs, and use the puncture method to measure 5×106 cells in the lungs of about 1 ml per ml mice After 3 weeks, the survival rate and tumor formation rate were counted, and the state of the mice was observed. T-PCR and Western Blot technology detect the expression of mRNA and protein in the resistance genes GST-π, P-gp170 and MMP-7 in tumors.

  Results: The drug resistance index of A549-Taxol lung cancer cells increased by 508 times, the expression of GST-π, P-gp170 and MMP-7 resistance proteins increased significantly (Pu003c0.001), and the invasion potential of lung cancer increased. A549-cells in the paclitaxel group Significantly higher than the A549 group. The viability and tumorigenicity of 5 × 106 cells injected into the lung with a 5 mm needle were 100. 85. After tumorigenesis, immunohistochemistry showed that the drug resistance protein was significantly expressed in the A549-Taxol group. Nude mice and resistance protein were higher than the A549 nude mice group.

  Conclusion: The expression of GST-π, P-gp170 and MMP-7 is related to paclitaxel resistance in lung cancer. An orthotopic animal model of lung cancer resistant to paclitaxel was established in advance. Drug-resistant cells are stable to drug-resistant paclitaxel and can be used for follow-up experimental studies.