Expression of heat shock protein 70 modulates the chemoresponsiveness of pancreatic cancer

Jong Jin Hyun, Hong Sik Lee, Bora Keum, Yeon Seok Seo, Yoon Tae Jeen, Hoon Jai Chun, Soon Ho Um, Chang Duck Kim

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    Background/Aims: Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. Methods: Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa- 2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. Results: HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. Conclusions: Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.

    Original languageEnglish
    Pages (from-to)739-746
    Number of pages8
    JournalGut and liver
    Volume7
    Issue number6
    DOIs
    Publication statusPublished - 2013 Nov

    Keywords

    • Gemcitabine
    • Heat shock proteins
    • Pancreatic neoplasms
    • Quercetin

    ASJC Scopus subject areas

    • Hepatology
    • Gastroenterology

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