Effect of 41°C and 43°C on cisplatin radiosensitization in two human carcinoma cell lines with different sensitivities for cisplatin

Abstract

The effect of trimodality treatment consisting of hyperthermia, cisplatin and radiation was investigated in two cell lines with different sensitivities to cisplatin. Hyperthermia treatment was performed for 1 h at 41˚C and 43˚C in order to compare the effects of the two temperatures. Clonogenic assays were performed with cisplatin-sensitive SiHa human cervical carcinoma and cisplatin-resistant SW-1573 human lung carcinoma cell lines. Cells were treated with various combinations of hyperthermia, cisplatin and radiation. Radiation was performed after 1 h of simultaneous hyperthermia and cisplatin treatment. Cisplatin exposure was for 1 h or continuous without refreshment of the cisplatin-containing medium. SiHa cells were more sensitive to cisplatin than SW-1573 cells. Hyperthermia at 41˚C decreased survival in SW-1573 cells but was not cytotoxic in SiHa cells. Hyperthermia at 43˚C decreased survival dramatically in both cell lines with SiHa being the most sensitive. The addition of hyperthermia at 41˚C and 43˚C to cisplatin treatment led to enhanced cell kill in both cell lines compared with cisplatin alone. Radiosensitization was observed after continuous but not after 1 h of cisplatin treatment. Hyperthermia at 43˚C increased radiosensitivity whereas hyperthermia at 41˚C did not. A combination of 41˚C hyperthermia with continuous cisplatin treatment had an additive effect on SW-1573 cells but enhanced cisplatin radiosensitivity of SiHa cells. In SW-1573 cells trimodality treatment using 43˚C hyperthermia enhances cisplatin radiosensitivity. We conclude that hyperthermia at 43˚C enhances cisplatin-induced radiosensitization in both cisplatin-sensitive and-resistant cell lines. Hyper-thermia at 41˚C was also able to increase cisplatin-induced radiosensitivity but only in the cisplatin-sensitive SiHa cell line.

Cell survival and radiosensitisation: Modulation of the linear and quadratic parameters of the LQ model

“…Cisplatin-based chemoradiotherapy has become standard treatment for, among others, locally advanced cervical carcinoma (30) and locally advanced non-small-cell lung cancer (NSCLC) (31). There have been numerous studies on the radiation-sensitising effect of cisplatin; however, the results vary from a clear cisplatin-induced radiosensitisation (24,25,(32)(33)(34) to a merely additive effect on cell survival (35). Cisplatin and radiation share a common cellular target, DNA (36).…”

“…The PLDR is reflected by the difference in survival between ip and dp cells. The inhibition of PLDR has been implicated in cisplatin-induced radiation sensitisation (25). More specifically, cisplatin-induced radiation sensitisation is caused by the inhibition of the non-homologous end joining (NHEJ) pathway and recombination repair (38,40,43).…”

“…Nonetheless, satisfactory results have been obtained in locally advanced cervical cancers treated with radiotherapy plus mild HT <43˚C (13). Mild temperatures may have more subtle effects than high temperatures, such as tumour reoxygenation (23)(24)(25)(26). We recently discovered that mild HT (42˚C for 1 h) transiently breaks down the BRCA2 protein (27).…”

“…In this section, the radiation sensitisation of cisplatin on the SW-1573 lung tumour cell line and the SiHa cervical tumour cell line is quantified by changes in the LQ parameters (25). Survival curves for SW-1573 lung tumour cells following radiation alone and radiation combined with cisplatin (1 µM for 1 h) are presented in Fig.…”

“…SW-1573 cells are derived from a human lung tumour and are much less sensitive to HT than RKO cells. Studies have been carried out to evaluate whether pre-treatment with HT at 41 or 43˚C can enhance the radiosensitivity of SW-1573 cells (25). HT at 41˚C for 1 h without irradiation did not result in a further decrease of the surviving fraction for ip and dp cells, compared to irradiation alone.…”