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Kyoshiro Takegahara



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    EP1.03 - Biology (ID 193)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.03-10 - Expression of Anti-Aging Gene, Klotho Is a Surrogate Marker of Pemetrexed for Lung Cancer Treatment (Now Available) (ID 296)

      08:00 - 18:00  |  Presenting Author(s): Kyoshiro Takegahara

      • Abstract
      • Slides

      Background

      Adjuvant chemotherapy using cisplatin is recommended for patients with lung cancer p-stage IB-IIIA, who were received surgical resection completely. In order to improve the prognosis of the patients with lung cancers, we need to find a new predictive factor for anti-cancer agents and establish a new regimen for the adjuvant chemotherapy. We have previously reported that anti-aging gene Klotho expression was a prognostic factor for small cell lung cancer and LCNEC so far. Therefore, in this study, we investigate the association between the expression of Klotho and the sensitivity against anti-cancer agents, and we examined the anti-tumor tumor effect of Klotho expression.

      Method

      We established a cell line, A549/Klotho, which stably overexpress Klotho, and then examined the association between the expression of Klotho and Epithelial-Mesenchymal Transition related proteins such as N-cadherin, E-cadherin, Snail, Vimentin, etc. Next, we performed the sensitivity test for various anticancer agents including pemetrexed, CDDP, paclitaxel, gefitinib, etc, using A549 cells and A549/Klotho cells. Moreover, we evaluated the role of Klotho expression against anti-tumor effect.

      Result

      By western blot analysis, the expression of N-cadherin was completely inhibited in A549/Klotho cells, but in A549 cells. This result suggested that Klotho expression may regulate the expression of N-cadherin and Klotho can play an important role in cancer metastasis/invasion by regulating EMT. Moreover, we clarified that miR145 was related to the inhibition of N-cadherin in analysis of A549/Klotho cells but not miR218, miR67. A549/Klotho cells were more sensitive seven times against pemetrexed compared to A549 cells (IC50; 0.1 micro M) by MTT assay. There is no difference of sensitivity between A549/Klotho cells and A549 cells against molecular target drugs such as gefitinib, other kinds of TKI.

      Conclusion

      From these results, we conclude that overexpression of Klotho may regulate the sensitivity against pemetrexed through the inhibition of expression of mir145 and N-cadherin. In the future, we may establish a new strategy of chemotherapy for patients with advanced lung cancer based on the expression of anti-aging gene Klotho.

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