Suppression of STAT3 by chemically modified siRNAs increases the chemotherapeutic sensitivity of parental and cisplatin-resistant non-small cell lung cancer cells

• Published in: Journal of B.U. ON. Vol. 19; no. 1; p. 145
• Main Authors: Tezcanli Kaymaz, Burcinn, Bozok Cetintas, Vildan, Eroglu, Zuhal, Kosova, Buket
• Format: Journal Article
• Language: English
• Published: Greece 01.01.2014
• Subjects: Apoptosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival; Cisplatin - administration & dosage; Drug Resistance, Neoplasm - genetics; Humans; RNA, Small Interfering - chemistry; RNA, Small Interfering - genetics; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism
• ISSN: 1107-0625

Increased activation of the JAK-STAT signaling pathway is frequently observed in several primary cancers as well as cancer cell lines. Thus, targeting JAK-STAT pathway components by different molecular-biologic approaches in the search for new anticancer therapies has become widespread and resulted in encouraging outcomes. In this study, the effects of chemically modified anti-STAT3 small interfering (si)RNAs on cell viability, proliferation and apoptosis of parental and cisplatin resistant non-small cell lung cancer (NSCLC) cells were investigated with the aim to provide a new therapeutic strategy for overcoming cisplatin resistance in lung cancer. The parental NSCLC cell line Calu1 and its cisplatin- resistant subline CR-Calu1 were used to study the effects of STAT3 suppression with chemically modified anti-STAT3 siRNAs. STAT3 gene and protein expressions were analyzed by real-time (RT) quantitative (q) PCR and Western blot, respectively. Apoptosis was evaluated by Caspase-3 activity and cell death assays. STAT3 messenger (m)RNA and protein expression were significantly increased in CR-Calu1 cells and suppressing its expression with specific siRNAs increased the rate of apoptosis through Caspase-3 activation. STAT3 suppression also significantly increased cisplatin sensitivity of Calu1 and CR-Calu1 cells after transfection with STAT3 siRNAs. NSCLC cells could be sensitized to cisplatin by targeting STAT3 with chemically modified siRNAs together, a fact which was accompanied with increased apoptosis.