Heat Shock Protein 27, a Novel Regulator of Transforming Growth Factor β Induced Resistance to Cisplatin in A549 Cell

Abstract

Lung cancer is one of the major causes of cancer morbidity and mortality around the world, and the resistance to cisplatin is a critical issue to chemotherapy in lung cancer patients. Transforming growth factor β (TGF-β) signal pathway abnormality is widely observed in drug resistance during lung cancer chemotherapy. Here, we investigated the effects of heat-shock protein 27 (HSP27) in the TGF-β-induced cisplatin resistance in lung cancer cell. In this study, our results indicated that the mRNA and protein expression of HSP27 were significantly increased in human lung cancer tissues. TGF-β induced the mRNA and protein expression of HSP27 in human lung cancer cell (A549). Treatment of TGF-β-induced cisplatin resistance in A549 cell through blocking the cisplatin-induced apoptosis and cell death, which characterized as the increasing of cell viability and decreasing of PARP and caspase3 cleavage in the cisplatin-treated cell. Knockdown of SMAD3 attenuated the TGF-β-induced HSP27 expression and restored the TGF-β-induced cisplatin resistance in A549 cell. Additionally, the knockdown of HSP27 blocked TGF-β-induced cisplatin resistance via decreasing cell viability and increasing cell apoptosis in A549 cell. These data therefore suggested that HSP27 is critical to lung cancer progression and TGF-β-induced cisplatin resistance in human lung cancer cell, and may provide an effective clinical strategy in lung cancer patients with resistance to chemotherapy.

Increased HSP27 correlates with malignant biological behavior of non-small cell lung cancer and predicts patient’s survival

“…Transforming growth factor β (TGF-β) signal pathway abnormality is widely observed in drug resistance during lung cancer chemotherapy. TGF-β induces the mRNA and protein expression of HSP27 in human lung cancer cell (A549) and the knockdown of HSP27 blocks TGF-β-induced cisplatin resistance via decreasing cell viability and increasing cell apoptosis in A549 cell 23 . It is reported that HSP27 is highly expressed in lung cancer tissues from mice, as well as in a lung cancer cell line.…”

“…Tissue microarray (TMA) blocks were prepared using lung cancer tissue and adjacent normal tissue from 76 lung cancer patients according to the method published previously 23 . The TMAs were constructed with a tissue array instrument (Beecher Instruments, Manual Tissue Arrayer, USA) by removal of a tissue core from the donor block using a thin-walled needle with an inner diameter of approximately 2.0 mm.…”

“…The expression of HSP27 in lung cancer tissues and adjacent normal tissues was tested by IHC method (Kit of Ultra-sensitive S-P; Fuzhou Maixin biotechnology company, China) according to a previous method that was described in published article 23 . The best dilution of anti-human HSP27 antibody is 1:100.…”

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

“…Blockage of TGF-β-mediated cisplatin resistance and decrease of cell viability, and increase of cell apoptosis by knockdown of HSP27 [99] Lung cancer stem cells…”

“…In laryngeal cancer cells, the overexpression of HSP27 exerts cellular resistance against various cytotoxic agents, such as cisplatin and staurosporin, by inducing cell cycle arrest and remodeling actin polymerization involved in drug uptake [97]. In lung cancer, HSP27 promotes TGF-β-induced cisplatin resistance through regulation of SMAD3 [99]. In particular, lung cancer stem cells showed decreased apoptotic response to treatment with superoxide, cisplatin, and gemcitabine when HSP27 was hyperactivated [100].…”