Heat shock protein 27 knockdown using nucleotide‑based therapies enhances sensitivity to 5-FU chemotherapy in SW480 human colon cancer cells.

Abstract

Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that is produced in response to various stresses and has a cytoprotective function. In the present study we found that there is a strong correlation between sensitivity to 5-fluorouracil (5-FU) and the expression of Hsp27 in colorectal cancer. Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various antitumor effects in some types of cancer, such as bladder and prostate. Although several clinical studies are currently studying apatorsen in many malignancies, to date no promising results have been reported for colorectal cancer. In the present study, we examined the impact of Hsp27 downregulation (via apatorsen) on 5-FU sensitivity in colon cancer both in vitro and in vivo. In vitro, apatorsen significantly decreased the levels of Hsp27 in a dose-dependent manner in human colon cancer SW480 cells. A cell proliferation assay revealed that although apatorsen did not inhibit tumor growth, it resulted in greater 5-FU sensitivity in comparison with treatment with OGX-411 (control). In vivo, intraperitoneal injection of apatorsen decreased the levels of Hsp27 in subcutaneous tumors in a xenograft mouse model using SW480 cells and enhanced 5-FU sensitivity, compared to controls. Although further research is warranted, the present study confirmed that concurrent treatment with Hsp27 knockdown using apatorsen and 5-FU could be a promising therapy for colon cancer.

• Authors: Takehiro Shimada, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Kohei Shigeta, Takashi Ishida, Yusuke Asada, Hirofumi Suzumura, Kaoru Koishikawa, Shingo Akimoto, Yuko Kitagawa
• Journal: Oncology reports (Oncol Rep) Vol. 39 Issue 3 Pg. 1119-1124 (Mar 2018) ISSN: 1791-2431 [Electronic] Greece
• PMID: 29328475 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Biomarkers, Tumor
• HSP27 Heat-Shock Proteins
• HSPB1 protein, human
• Heat-Shock Proteins
• Molecular Chaperones
• Oligonucleotides, Antisense
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Apoptosis
• Biomarkers, Tumor
• Cell Proliferation
• Colonic Neoplasms (drug therapy, genetics, pathology)
• Drug Resistance, Neoplasm (genetics)
• Fluorouracil (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• HSP27 Heat-Shock Proteins (antagonists & inhibitors, genetics)
• Heat-Shock Proteins
• Humans
• Mice
• Mice, SCID
• Molecular Chaperones
• Oligonucleotides, Antisense (administration & dosage)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays