Grimmig Tanja, Moll Eva-Maria, Kloos Kerstin, Thumm Rebecca, Moench Romana, Callies Simone, Kreckel Jennifer, Vetterlein Malte, Pelz Joerg, Polat Buelent, Tripathi Sudipta, Rehder Roberta, Ribas Carmen M, Chandraker Anil, Germer Christoph-T, Waaga-Gasser Ana Maria, Gasser Martin
Department of Surgery I, Molecular Oncology and Immunology, University of Wuerzburg, Wuerzburg, Germany.
Division of Molecular Internal Medicine, Department of Internal Medicine II, University of Wuerzburg, Wuerzburg, Germany.
Cancer Growth Metastasis. 2017 Sep 18;10:1179064417730559. doi: 10.1177/1179064417730559. eCollection 2017.
In patients with peritoneal carcinomatosis cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment strategy. Here, we studied the role of hyperthermic chemotherapy on heat shock protein (HSP) expression and induction of tumor cell death and survival. HSP27, HSP70, and HSP90 combined with effects on tumor cell proliferation and chemosensitivity were analyzed in human colon cancer. Hyperthermic chemotherapy resulted in significant HSP27/HSP70 and HSP90 gene/protein overexpression in analyzed HT-29/SW480/SW620 colon cancer cells and peritoneal metastases from patients displaying amplified expression of proliferation markers, proliferating cell nuclear antigen and antiapoptotic protein Bcl-xL. Moreover, functionally increased chemoresistance against 5-fluorouracil/mitomycin C and oxaliplatin after hyperthermic chemotherapy points to induced survival mechanisms in cancer cells. In conclusion, the results indicate that intracellular HSP-associated antiapoptotic and proliferative effects after hyperthermic chemotherapy negatively influence beneficial effects of hyperthermic chemotherapy-induced cell death. Therefore, blocking HSPs could be a promising strategy to further improve the rate of tumor cell death and outcome of patients undergoing HIPEC therapy.
对于伴有腹膜癌转移的患者，细胞减灭术联合腹腔内热化疗（HIPEC）是一种很有前景的治疗策略。在此，我们研究了热化疗对热休克蛋白（HSP）表达以及肿瘤细胞死亡和存活诱导的作用。分析了HSP27、HSP70和HSP90在人结肠癌中对肿瘤细胞增殖和化疗敏感性的联合影响。热化疗导致在分析的HT-29/SW480/SW620结肠癌细胞以及来自显示增殖标志物、增殖细胞核抗原和抗凋亡蛋白Bcl-xL表达增加的患者的腹膜转移灶中，HSP27/HSP70和HSP90基因/蛋白显著过表达。此外，热化疗后对5-氟尿嘧啶/丝裂霉素C和奥沙利铂的化疗耐药性在功能上增加，这表明癌细胞中诱导了存活机制。总之，结果表明热化疗后细胞内HSP相关的抗凋亡和增殖作用对热化疗诱导的细胞死亡的有益效果产生负面影响。因此，阻断HSP可能是进一步提高肿瘤细胞死亡率和接受HIPEC治疗患者预后的一种有前景的策略。
