Author of

• 11515

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  P2.05 - Poster Session 2 - Preclinical Models of Therapeutics/Imaging (ID 158)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11529

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    P2.05-014 - Schedule-dependent Interactions between Pemetrexed and Vinorelbine in Human Lung Cancer Cells (ID 2387)

    09:30 - 09:30  |  Author(s): R. Kiefl
    • Abstract

    Background
    Lung cancer is the leading cause of cancer deaths worldwide. Despite advances and progresses in surgery, chemotherapy, and radiotherapy over the last decades, the death rate from lung cancer has remained largely unchanged, which is mainly due to metastatic disease and multi drug resistance. Because of the overall poor prognosis, new treatment strategies for lung cancer patients are urgently needed. The aim of this study was to investigate the interactions between pemetrexed and vinorelbine for human adenocarcinoma via various chemotherapy schedules.

    Methods
    HCC cells and cisplatin resistant HCC cells (HCC-res) were treated with different schedules of combination of cisplatin (Cis), vinorelbine (Vin), and pemetrexed (Pem) respectively, more specific as Cis, Vin, Pem, Cis+Vin, Cis+Pem, Vin+Pem, Vin→Pem, Pem→Vin, Cis+Vin+Pem, Cis→Pem→Vin, and Cis→Vin→Pem. Cell growth inhibition was determined by cell viability analysis. Cell apoptosis was analyzed via annexin V staining and FACS analysis. And cytoplasm Ca[2+] was measured with Ca[2+] indicator dye Fura-2 AM.

    Results
    Vin and Pem caused a strong dose-dependent cytotoxic effect in both HCC and HCC-res cells. The IC50 values of Vin against HCC and HCC-res cells were 10.34 ± 1.12 nM and 9.98 ±2.12 nM, respectively. The IC50 values of Pem against these cells were 110.77 ± 17.28 nM and 118.89 ±18.77 nM respectively. The application of different therapy schedules induced a significant time dependent cell growth inhibition on HCC naïve and cisplatin resistant cells. The therapy scheme of Cis→Pem→Vin showed the strongest inhibitory effect on both HCC and HCC-res cells. The application of different therapy schedules on HCC and HCC-res cells increased the percentage of cells undergoing apoptosis, except the application of Vin alone. In both HCC and HCC-res cells, Cis→Pem→Vin was found the most effective to induce apoptosis. The application of different therapy schedules on HCC and HCC-res cells increased [Ca[2+]]~c~. Only the application of Vin alone failed to increase [Ca[2+]]~c~ in HCC cells. The most elevated [Ca[2+]]~c ~was found in the cells treated with Cis→Pem→Vin in both HCC and HCC-res cells

    Conclusion
    We demonstrated that the sequential application of Cis, Vin and Pem has a synergistic effect in cell growth inhibition, apoptosis induction, and [Ca[2+]]~c~ elevation in HCC and HCC-res cells. The Ca[2+ ]overload could lead to apoptosis, which was related to the cell growth inhibitory effect of chemotherapeutics in lung cancer cells. It might cast a light to develop chemotherapy schedules for patients, and to overcome cisplatin resistance in lung cancer.