Inhibition of Src family kinases overcomes anoikis resistance induced by spheroid formation and facilitates cisplatin-induced apoptosis in human mesothelioma cells

  • Authors:
    • Ryoji Eguchi
    • Yumiko Fujita
    • Chiharu Tabata
    • Hiroyasu Ogawa
    • Ichiro Wakabayashi
    • Takashi Nakano
    • Yoshihiro Fujimori
  • View Affiliations

  • Published online on: August 13, 2015     https://doi.org/10.3892/or.2015.4200
  • Pages: 2305-2310
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Malignant mesothelioma is an aggressive tumor arising from mesothelial cells of serous membranes, and forms spheroid-like cell aggregates in pleural and peritoneal effusions. We examined the levels of anoikis, apoptosis induced by the detachment of cells from the extracellur matrix, in suspension culture in the human mesothelioma cell line NCI-H2052. NCI-H2052 cells were adherent in conventional monolayer cultures, but were found to form spheroids in suspension cultures using dishes with ultra-low cell binding capacity. NCI-H2052 cells proliferated in both cultures, but the proliferation rate was markedly lower in suspension cultures than in monolayer cultures. In addition, NCI-H2052 cells in suspension cultures showed little apoptosis, suggesting that the suspension culture induces anoikis resistance. Western blot analysis revealed that suspension cultures induced activation of Src family kinases (SFK) after spheroid formation. Dasatinib, an inhibitor of multi-tyrosine kinases including SFK, abolished anoikis resistance in suspension cultures, indicating that SFK activated by spheroid formation are responsible for anoikis resistance. Cisplatin induced apoptosis in NCI-H2052 cells, but the apoptotic rate was significantly lower in suspension cultures than in monolayer cultures, suggesting that spheroid formation is involved in cisplatin resistance. Furthermore, a combination of dasatinib and cisplatin induced apoptosis more significantly than either alone in suspension cultures. These results suggest that spheroid formation induces resistance to anoikis and to cisplatin through SFK activation and that dasatinib facilitates cisplatin-induced apoptosis in human mesothelioma cells.
View Figures
View References

Related Articles

Journal Cover

November-2015
Volume 34 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Eguchi R, Fujita Y, Tabata C, Ogawa H, Wakabayashi I, Nakano T and Fujimori Y: Inhibition of Src family kinases overcomes anoikis resistance induced by spheroid formation and facilitates cisplatin-induced apoptosis in human mesothelioma cells. Oncol Rep 34: 2305-2310, 2015.
APA
Eguchi, R., Fujita, Y., Tabata, C., Ogawa, H., Wakabayashi, I., Nakano, T., & Fujimori, Y. (2015). Inhibition of Src family kinases overcomes anoikis resistance induced by spheroid formation and facilitates cisplatin-induced apoptosis in human mesothelioma cells. Oncology Reports, 34, 2305-2310. https://doi.org/10.3892/or.2015.4200
MLA
Eguchi, R., Fujita, Y., Tabata, C., Ogawa, H., Wakabayashi, I., Nakano, T., Fujimori, Y."Inhibition of Src family kinases overcomes anoikis resistance induced by spheroid formation and facilitates cisplatin-induced apoptosis in human mesothelioma cells". Oncology Reports 34.5 (2015): 2305-2310.
Chicago
Eguchi, R., Fujita, Y., Tabata, C., Ogawa, H., Wakabayashi, I., Nakano, T., Fujimori, Y."Inhibition of Src family kinases overcomes anoikis resistance induced by spheroid formation and facilitates cisplatin-induced apoptosis in human mesothelioma cells". Oncology Reports 34, no. 5 (2015): 2305-2310. https://doi.org/10.3892/or.2015.4200