Optimal combination chemotherapy and chemoradiotherapy with etoposide for advanced cervical squamous cancer cells in vitro

  • Authors:
    • Tetsuji Tanaka
    • Tao Bai
    • Kazunori Yukawa
    • Naohiko Umesaki
  • View Affiliations

  • Published online on: April 1, 2006     https://doi.org/10.3892/or.15.4.939
  • Pages: 939-947
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Abstract

Patients with unresectable advanced carcinoma of the uterine cervix are usually treated with chemotherapy or chemoradiotherapy. In the present study, the optimal administration protocol for etoposide in chemotherapy and chemoradiotherapy for advanced cervical cancer patients was investigated in vitro using the radio-sensitive and anticancer drug-sensitive human cervical squamous cell carcinoma cell line ME180. Therapeutic doses of concurrent irradiation reduced the cellular etoposide sensitivity in a dose-dependent manner, while postirradiation-surviving subclones established from repeatedly irradiated ME180 cells showed significantly higher etoposide sensitivities than the non-irradiated parent cells. Of the 6 monoclonal etoposide-resistant subclones established from ME180 cells, 5 were significantly radioresistant. Although the etoposide-resistant subclones were also significantly resistant to other anticancer drugs, such as cisplatin, carboplatin, nedaplatin, pirarubicin, paclitaxel and docetaxel, they were more sensitive to 5-fluorouracil, mitomycin C and SN38 than the parent cells. Flow cytometric analyses revealed that the etoposide-resistant subclones showed significantly increased cell surface expression of CD40 compared to the parent cells, which expressed undetectable levels of CD40. However, the expression of some integrin receptor subunits, such as CD29, CD49a and CD49f, was apparently reduced in the etoposide-resistant subclones. These results indicate that etoposide should be administered to advanced cervical squamous cancer patients after the completion of radiotherapy, rather than as a concurrent chemoradiotherapy. In order to kill surviving etoposide-resistant cancer cells more effectively, 5-fluorouracil, mitomycin C and irinotecan may be candidate combination drugs for use with etoposide. Differential expression of integrin receptors and CD40 may be involved in the acquisition of etoposide resistance by cervical squamous cancer cells.

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April 2006
Volume 15 Issue 4

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

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Spandidos Publications style
Tanaka T, Bai T, Yukawa K and Umesaki N: Optimal combination chemotherapy and chemoradiotherapy with etoposide for advanced cervical squamous cancer cells in vitro. Oncol Rep 15: 939-947, 2006
APA
Tanaka, T., Bai, T., Yukawa, K., & Umesaki, N. (2006). Optimal combination chemotherapy and chemoradiotherapy with etoposide for advanced cervical squamous cancer cells in vitro. Oncology Reports, 15, 939-947. https://doi.org/10.3892/or.15.4.939
MLA
Tanaka, T., Bai, T., Yukawa, K., Umesaki, N."Optimal combination chemotherapy and chemoradiotherapy with etoposide for advanced cervical squamous cancer cells in vitro". Oncology Reports 15.4 (2006): 939-947.
Chicago
Tanaka, T., Bai, T., Yukawa, K., Umesaki, N."Optimal combination chemotherapy and chemoradiotherapy with etoposide for advanced cervical squamous cancer cells in vitro". Oncology Reports 15, no. 4 (2006): 939-947. https://doi.org/10.3892/or.15.4.939