Increasing Colorectal Cancer Cell Sensitivity To Oxaliplatin Through Hyperthermia And Chloroquine Treatment

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2016)

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摘要
Colorectal cancer is the third most lethal form of cancer worldwide, with most patients dying of liver metastases. Patients with metastatic livers can be treated with hyperthermia therapy, which often uses IHP (Isolated Hepatic Perfusion). Hyperthermia has become as a highly anticipated method. Using traditional hyperthermia alone is unable to inhibit tumor cell proliferation. Tumor can be inhibited effectively by combining oxaliplatin with a 42 degrees C hot water bath. However, this combination has been shown to induce autophagy in colorectal cancer cell lines, which inhibits tumor cell death to some extent. In order to combat this problem, we used oxaliplatin in combination with autophagy inhibitor chloroquine (CQ) at 42 degrees C. We found that oxaliplatin combined with CQ at 42 degrees C induces caspase-dependent apoptosis in colorectal cancer cells. This treatment not only impacts BCL-2 family proteins, but also downregulates the HSP and IAP family proteins. Activated caspase and PRAP (poly ADP-ribose polymerase) proteins are all upregulated. The results are suggesting that oxaliplatin combined with CQ at 42 degrees C is a novel anti-tumor approach against colorectal cancer.
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关键词
Colorectal cancer, hyperthermia, oxaliplatin, chloroquine, apoptosis, autophagy
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