onnexin 43对非小细胞肺癌细胞吉非替尼原发性耐药的影响

im: To investigate relationship between connexin 43 (Cx43) expression and non small cell lung cancer (NSCLC) with primary resistance to gefitinib. Methods: Gefitinib efficacy in A549 cells and Calu3 cells was detected by MTT assay. The protein expression of Cx43 and phospho-Akt (p-Akt) was detected by Western blot. The functional gap junction intercellular communication (GJIC) was measured by "parachute" assay. The cellular localization of Cx43 protein was evaluated by immunofluorescence staining. Results: MTT assay showed that gefitinib cytotoxicity in Calu3 cells is significantly less than that in A549 cells with IC50 of 0.064±0.011 μM versus 13.64±0.015 μM, respectively. Expression of Cx43 in Calu3 cells was significantly lower than that in A549 cells (P＜0.01). Moreover, p-Akt protein in Calu3 cells is obviously lower than that in A549 cells (P＜0.01). Furthermore, functional GJIC was found in A549 with or without RA (a well-defined GJIC enhancer) treatment, but not in Calu3 cells. Immunofluorescence staining clearly showed that Cx43 protein differentially accumulates in the membrane of A549 cells and the cytoplasm of Calu3 cells. Conclusion: Upregulation of Cx43 in membrane of A549 cells may contribute to the primary resistance to gefitinib by GJIC-dependent activation of PI3K/Akt signaling pathway.