Heat-shock protein 27 plays the key role in gemcitabine-resistance of pancreatic cancer cells.

Abstract

Pancreatic cancer is one of the most fatal types of cancer in developed countries. Most patients have locally advanced or metastatic cancerous lesions when they are diagnosed, due to the progressive, invasive and metastatic capacity of this disease to liver, lymph nodes and distant organs during early stages. Although the only curative therapy is complete surgical resection, the disease has usually already progressed by the time of diagnosis, and the majority of patients have metastatic disease. Therefore, palliative chemotherapy remains the only therapy for patients with progressive disease. Gemcitabine has been used for pancreatic cancer as the most effective anticancer drug. However, there are many cases resistant to gemcitabine. Thus, a better understanding of the molecular mechanisms of resistance to gemcitabine is essential to allow it to be used more effectively. Our previous proteomic studies demonstrated that the expression of heat-shock protein 27 (HSP27) was increased in gemcitabine-resistant pancreatic cancer cells and this might play a role in determining the sensitivity of pancreatic cancer to gemcitabine. Increased HSP27 expression in tumor specimens was related to resistance to gemcitabine and a shorter survival period in patients with pancreatic cancer. Furthermore, it has been shown that treatment strategies combining the HSP inhibitor KNK437 or interferon-γ (IFN-γ) with gemcitabine, were effective in gemcitabine-resistant pancreatic cancer cells in vitro. Furthermore, combined therapy of gemcitabine with IFN-γ of gemcitabine-resistant pancreatic cancer-bearing nude mice showed synergistic therapeutic effects on gemcitabine-resistant pancreatic cancer bearers. In this review, we summarize the current understanding of HSP27 and its role in gemcitabine resistance.

• Authors: Yasuhiro Kuramitsu, Yufeng Wang, Kumiko Taba, Shigeyuki Suenaga, Shomei Ryozawa, Seiji Kaino, Isao Sakaida, Kazuyuki Nakamura
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 6 Pg. 2295-9 (Jun 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22641665 (Publication Type: Journal Article, Review)

Chemical References

• Antimetabolites, Antineoplastic
• HSP27 Heat-Shock Proteins
• Deoxycytidine
• Gemcitabine

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Deoxycytidine (analogs & derivatives, pharmacology)
• Drug Resistance, Neoplasm (physiology)
• HSP27 Heat-Shock Proteins (metabolism)
• Humans
• Pancreatic Neoplasms (metabolism)
• Proteomics
• Gemcitabine