In vitro concurrent paclitaxel and radiation of four vulvar squamous cell carcinoma cell lines

Abstract

BACKGROUND.The antitubule agent paclitaxel causes a cell cycle blockage in the most radiosensitive part of the cell cycle, the GJM phase. The possible radiosensitizing effect of paclitaxel was tested in four vulvar (UM-SCV-lA, UM-SCV-lB, UM-SCV-2, and UM-SCV-4) squamous cell carcinoma (SCC) cell lines. METHODS. A 96-well plate clonogenic assay was performed with paclitaxel and radiation, both separately and concomitantly. Survival data were fitted to the linear quadratic model. The area under the curve, equivalent to the mean inactivation dose (D), was obtained by numerical integration. The effect of paclitaxel on radiosensitivity was measured as the AUC ratio (paclitaxel plus radiation: radiation alone). This ratio was compared with the surviving fraction (SF,) after paclitaxel alone. RESULTS. Paclitaxel concentrations of 0.4 to 2.0 nanomolar (nM) caused 1 to 70% inhibition of clonogenic survival. The AUC values of the cell lines were 1.9 to 2.9 gray. A full additive effect was observed when paclitaxel and radiation were administered concurrently; however, a supra-additive effect never occurred. The type of paclitaxel radiation interaction was not affected by the concentration of the drug nor did the type of interaction vary between cell lines studied. CONCLUSIONS. Paclitaxel and radiation used concomitantly produced a clear additive effect at all concentrations and in all Vulvar carcinoma cell lines tested. Although no supra-additive effect was observed, the additive effect already in nM concentrations could be beneficial in clinical use and, therefore, requires further investigation.

Supra‐additive effect with concurrent paclitaxel and cisplatin in vulvar squamous cell carcinoma in vitro

“…The difference between the cell lines is only 3‐fold. Paclitaxel sensitivities of 4 of the cell lines were reported previously,19 and UT‐SCV‐3 was tested for this study. The IC 50 value of the UT‐SCV‐3 was 1.5 nM, and all the paclitaxel IC 50 values varied between 0.6 and 1.7 nM (Table II), similarly showing a 2.8‐fold difference between the cell lines.…”

“…In the current study, a 24‐hr exposure of paclitaxel prior to cisplatin was used. Paclitaxel exposure of 24 hr before subsequent cisplatin administration or radiation has also been used in our previous studies with ovarian cancer cell lines and chemoradiation studies with vulvar SCC 19, 25. These 2 cytotoxic agents have different mechanisms of action,22, 23 but the mechanism of this sequence‐dependent interaction has not yet been clarified.…”

“…However, both cisplatin and paclitaxel have established efficacy in single‐agent use in SCC cell lines in vitro 16–18. Previously, we found vulvar SCC cell lines to be sensitive to paclitaxel in nanomolar concentrations and also demonstrated an additive effect when paclitaxel was combined with ionizing radiation 19–21. Paclitaxel and cisplatin have considerably different mechanisms of action.…”

The effects of narrow-band middle infrared radiation in enhancing the antitumor activity of paclitaxel

“…Combining pelvic radiation therapy with paclitaxel is effective for patients with muscle invasive transitional cell carcinoma of the urinary bladder (Nichols et al, 2000). Moreover, administering ionizing radiation and paclitaxel concurrently has been shown to have additive effects in vulvar carcinoma cell lines and human cervical carcinoma cells (Geard and Jones, 1994;Jaakkola et al, 1996). However, determining the optimum dosage and administration schedule of this combination therapy will require further investigation.…”

Combining taxanes with radiation for solid tumors

“…Docetaxel also has been shown to enhance response to radiation with induced mitotic arrest and apoptosis in murine tumor cells [12, 19]. The effects of taxane exposure have been studied with numerous human cell lines derived from tumors of the lung [15, 20–23], head and neck [24–27], brain [28, 17, 18], breast [15, 20, 29, 22], colon [29], pancreas [15], ovary [15, 20, 30], cervix [14, 25, 16, 31], vulva [32], and prostate [33, 29], and from melanoma [21] and leukemia [13] cells. A supra‐additive effect was observed most frequently, but additive or subadditive effects also were demonstrated under some experimental conditions.…”