| Summary: | 碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 99 === The cellular prion protein (PrPc) is highly conserved in mammalian species, and implicated to play essential role in physiological functions. Although the abnormal and protease-resistant-scrapie form (PrPsc) has been clearly demonstrared to be involved in the prion disease, the cellular function of PrPc remains unclear. In our previous study, PrPc expression has been shown to be higher in invasive pulmonary adenocarcinoma tumors compared to in situ tumors. Furthermore, knockdown of PrPc expression in the highly invasive lung adenocarcinoma cell line CL1-5 reduces its invasive ability. Together, our results indicate that PrPc may participate in the pathogenetic mechanism of lung adenocarcinoma invasion/ metastasis. In this study, we investigate whether the expression of PrPc is correlated with drug resistance in non-small cell lung cancer. We found that there is no correlation between PrPc levels and multidrug resistance scores in established lung adenocarcinoma cell lines. We manipulated PrPc expression levels in lung cancer cell lines, and tested the effect on sensitivity to anti-cancer drugs. The data showed that manipulate prion in most lung cancer cell lines we examined didn’t affect their drug resistance. With some exception, knockdown of PrPc expression in H23 cells caused a slight increase in the resistance to Pemetrexed. On the other hand, knockdown of PrPc expression in CL1-5 cells (CL1-5 PRNPi) sensitized cells to anti-tubulin drugs, including Paclitaxel, Docetaxel and Vinorelbine. Although resistance to anti-tubulin agents has been demonstrated to associate with high p-glycoprotein levels, we detected no change of p-glycoprotein levels in CL1-5 PRNPi cells when compared to control cells. Therefore, the sensitivity to anti-tubulin drugs in CL1-5 PRNPi cells is likely p-glycoprotein independent. Taken together, there is no correlation between PrPc and drug resistance in non-small cell lung cancer, but PrPc may affect drug resistance in some types of lung cancer cells and the molecular mechanism remains to be elucidated.
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