Anticancer Drug Sensitivity Test on Squamous Cell Carcinoma Cell Lines Derived From Human Oral Cancers: Optimal Contact Concentrations of CDDP and 5-FU Using the CD-DST

Introduction： The collagen gel droplet embedded culture drug sensitivity test (CD-DST) is an anticancer drug sensitivity test that uses a method of three-dimensional culture of very small samples, and it is suited to primary culture of human cancer cells. It is a useful method for oral squamous cell carcinoma (OSCC), in which the cancer tissues needed for testing are in limited supply. However, as the optimal contact concentrations of anticancer drugs for OSCC treatment have yet to be established, CD-DST for OSCC is currently carried out by applying the optimal contact concentrations for stomach cancer. Squamous carcinoma cell lines from human oral cancer were used to investigate the optimal contact concentrations of cis-diammine dichloroplatinum (CDDP) and 5-fluorouracil (5-FU) in performing CD-DST for OSCC in the present study.

 Materials and Methods：CD-DST was performed on seven squamous cell carcinoma cell lines derived from human oral cancers were used: SAS (squamous cell carcinoma of the tongue), Ca9-22 (squamous cell carcinoma of the gingiva), HO-1-N-1 (squamous cell carcinoma of the buccal mucosa), HSC-3 (squamous cell carcinoma of the tongue), HSC-4 (squamous cell carcinoma of the tongue), OSC-19 (squamous cell carcinoma of the tongue), and KON (squamous cell carcinoma of the floor of the mouth).  using CDDP and 5-FU in graded concentrations, and the optimal contact concentrations were calculated from the clinical response rate of OSCC to single drug treatment and the in vitro efficacy rate curve.

Results：The optimal concentrations were 0.5 µg/mL for CDDP and 0.7 µg/mL for 5-FU. The anti-tumour efficacy of CDDP at this optimal contact concentration using the CD-DST was compared to that using the clinically equivalent dose (CED) nude mouse method. The results of treating nude mice bearing these tumours with CDDP at the CED were compared with the CD-DST results for the same cell lines of CDDP administered at the optimal contact concentration (0.5 µg/mL). The T/C values from CD-DST were: Ca9-22, 67.3%; SAS, 61.7%; and OSC-19, 86.6%. The T/C values from the nude mouse CED method were: Ca9-22, 64.6%; SAS, 65.6%; and OSC-19, 64.0%. The T/C values obtained from the two different methods were roughly equal. Conclusion：The resistance genes of seven cell lines were checked by RT-PCR, and the cell lines were used to estimate the optimal contact concentration of CDDP and 5-FU in OSCC treatment. The optimal contact concentrations were 0.5 µg/mL for CDDP and 0.7 µg/mL for 5-FU. The results of the anticancer drug sensitivity test for CDDP at the calculated optimal contact concentration agreed with the nude mouse method results, implying that the optimal contact concentration is appropriate. The reproducibility of the optimal contact concentration needs to be investigated clinically by comparing optimal contact concentrations and treatment results.

References：

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2)       Nagai N, Minamikawa K, Mukai K, Hirata E, Komatsu M and Kobayashi H: Predicting the chemosensitivity of ovarian and uterine cancers with the collagen gel droplet culture drug-sensitivity test. Anti-Cancer Drug 16: 525-531, 2005.