gms | German Medical Science

Introduction: In patients with peritoneal carcinomatosis (PC) from gastrointestinal cancer hyperthermic intraperitoneal chemoperfusion (HIPEC) represents a treatment option integrated into multimodal concepts. In order to optimize current HIPEC conditions we analyzed different perfusion temperatures and chemotherapeutic effects in vitro and compared with observations in tumors from patients with PC.

Material and methods: Patients with PC from adenocarcinomas that underwent HIPEC therapy in our department were included in the study. HIPEC therapy was performed under standard conditions (1hr permanent chemotherapeutical flux via external pump into the abdominal cavity after resection of relevant tumor masses with elevated temperature between 41 and 43°C). Tumors before and after HIPEC therapy were analyzed for relevant molecular targets. Additionally, HT29 tumor cells were exposed in vitro to different hyperthermic conditions and comparably analyzed. Tumor cells were studied for apoptosis.

Results: Heat Schock Protein (HSP70/72, HSP90) and CD133 expression for analysis of resistence mechanisms was upregulated in the investigated tumors after HIPEC. Upregulated protein and gene expression was additionally shown for Multi Drug Resistance (MDR) genes ABCB5, ABCG2 and ABCC5. Hyperthermia induced upregulated protein and gene expression in HT29 colon cancer cells dependent on incubation temperatures, mainly for HSPs observed in Western blot, immunohistochemistry and RT-qPCR. Furthermore, cell viability decreased with increasing incubation temperature. However, careful adjustment of hyperthermia with combinational 5-FU chemotherapy was necessary for achieving optimized tumor cell cytotoxicity.

Conclusion: Therapeutic approaches like HIPEC to achieve antiproliferative and apoptosis inducing cellular effects in patients with PC seem to be negatively influenced by highly conserved HSP mechanisms as well as multidrug resistance genes. Studying HSP and MDR expression profiles both in patient tumors and in vitro are valuable tools to further clarify the effects of hyperthermia and chemotherapeutical agents in the context with HIPEC in affected PC patients.