Secreted phosphoprotein-1(SPP1) contributes to second generation EGFR tyrosine kinase inhibitor resistance in non-small cell lung cancer.

In this study, we established afatinib acquired resistant cell lines. Gene array technology was used to screen changes in gene expression between afatinib-resistant lung cancer cells and parental cells. Our results showed that secreted phosphoprotein-1 (SPP1) was significantly increased in afatinib-resistant lung cancer cells. To study the effect of SPP1 on afatinib resistance, siSPP1 was used to knockdown SSP1 in afatinib-resistant lung cancer cells. Then sensitivity to afatinib and invasive ability were studied. We found that knockdown of SPP1 increased sensitivity of lung cancer cells to afatinib and decease the ability of invasion. Of clinical significance, we found that SSP1 was up-regulated in lung cancer tissues compared with adjacent normal tissues, and low level of SSP1 was strongly associated with better overall survival. Our results suggest that SPP1 enhanced the second generation EGFR TKI resistance in lung cancer, and inhibiting SPP1 might be a therapeutic target to overcome afatinib resistance. PMID: 30832751 [PubMed - as supplied by publisher]
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research