Cisplatin resistance induced by decreased apoptotic activity in non‐small‐cell lung cancer cell lines

Çetintaş, Vildan Bozok; Küçükaslan, Ali Şahin; Kosova, Buket; Tetik, Asli; Selvi, Nur; Çok, Gürsel; Gündüz, Cumhur; Eroğlu, Zühal

doi:10.1042/cbi20110329

Cited by 37 publications

(27 citation statements)

References 6 publications

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“…It is well-established that p53 plays a central role in cisplatin-induced apoptosis independent of caspase-8 [13][14][15]. Similarly, we observed that cisplatin caused 10% cell death in A549 and H522 cells regardless of c-Src or caspase-8, which was prevented from the pancaspase inhibitor, zVAD-fmk ( Fig.…”

Section: C-src-induced Caspase-8 Phosphorylation In Lung Adenocarcinosupporting

confidence: 66%

Dasatinib promotes paclitaxel-induced necroptosis in lung adenocarcinoma with phosphorylated caspase-8 by c-Src

Diao

Wang

et al. 2016

Cancer Letters

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Section: C-src-induced Caspase-8 Phosphorylation In Lung Adenocarcinosupporting

confidence: 66%

Dasatinib promotes paclitaxel-induced necroptosis in lung adenocarcinoma with phosphorylated caspase-8 by c-Src

Diao

Wang

et al. 2016

Cancer Letters

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“…A cisplatin-resistant subline of A549 and a gefitinib-resistant subline of PC9 were established by repeated subculturing with gradual increasing in the cisplatin (2, 4, 6, 8 and 10 μ M) or gefitinib concentration (4, 8, 16, 20 and 40 μ M) over a 3-month period. 52 In addition, A549, PC9, SW480 and SKCO1 cell lines with stable overexpression or knockdown of ZNF32 were constructed as described previously. 35 …”

Section: Methodsmentioning

confidence: 99%

ZNF32 contributes to the induction of multidrug resistance by regulating TGF-β receptor 2 signaling in lung adenocarcinoma

et al. 2016

Cell Death Dis

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Multidrug resistance (MDR) is one of the most important contributors to the high mortality of cancer and remains a major concern. We previously found that zinc finger protein 32 (ZNF32), an important transcription factor associated with cancer in Homo sapiens, protects tumor cells against cell death induced by oxidative stress and other stimuli. We thus hypothesized that ZNF32 might enable the tolerance of cancer cells to anti-tumor drugs because higher ZNF32 expression has been found in cancer tissues and in drug-resistant lung adenocarcinoma (AC) cells. In this study, we found that ZNF32 is upregulated by Sp1 (specificity protein 1) in response to drug treatment and that ZNF32 promotes drug resistance and protects AC cells against cisplatin or gefitinib treatment. ZNF32 overexpression in AC cells conferred resistance to EGFR (epidermal growth factor receptor) inhibitors by enhancing MEK/ERK activation. Moreover, ZNF32 was found to directly bind to the TGF-βR2 (transforming growth factor-beta receptor 2) promoter to promote its expression, and ZNF32-induced resistance was mediated by enhancing TGF-βR2 expression and activating the TGF-βR2/SMAD2 pathway. In both a mouse model and ex vivo cultured patient samples, a high level of ZNF32 expression was closely associated with worse overall survival and cisplatin resistance. ZNF32 appears to be a potential inducer of drug resistance that could increase the expression of the drug resistance-associated gene TGF-βR2 and subsequently facilitate the induction of drug resistance during both conventional chemotherapy and novel target therapy. Thus, ZNF32-associated target therapy is a potential novel adjuvant therapy that might effectively prevent the occurrence of multidrug resistance (MDR) during chemotherapy and improve the survival of patients with AC.

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“…These mechanisms of resistance primarily involve the abnormal expression of drug transporters and drug metabolizing enzymes in cells (25), increased DNA damage repair (26), abnormal regulation of cell cycle and apoptosis-related protein expression (27).…”

Section: Discussionmentioning

confidence: 99%

Role of gambogic acid and NaI131 in A549/DDP cells

et al. 2016

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Abstract. Resistance to platinum in tumor tissue is a considerable barrier against effective lung cancer treatment. Radionuclide therapy is the primary adjuvant treatment, however, the toxic side effects limit its dosage in the clinical setting. Therefore, the present study aimed to determine whether an NaI 131 radiosensitizer could help reduce the toxic side effects of radionuclide therapy. In vitro experiments were conducted to determine whether NaI 131 can inhibit platinum resistance in A549/DDP cells, which are cisplatin-resistant non-small cell lung cancer cells, and whether gambogic acid (GA) is an effective NaI 131 radiosensitizer. Cell proliferation following drug intervention was analyzed using MTT and isobolographic analysis. Apoptosis was assessed by flow cytometry. In addition, the mechanisms of drug intervention were analyzed by measuring the expression of P-glycoprotein (P-gP), B cell lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax) and P53 using western blot analysis and immunocytochemistry. According to isobolographic analysis, a low concentration of NaI 131 combined with GA had a synergistic effect on the inhibition of A549/DDP cell proliferation, which was consistent with an increased rate of apoptosis. Furthermore, the overexpression of Bax, and the downregulation of P-gP, P53 and Bcl-2 observed demonstrated the potential mechanism(s) of NaI 131 and GA intervention. NaI 131 may induce apoptosis in A549/DDP cells by regulating apoptosis-related proteins. A low concentration combination of NaI 131 and GA was able to significantly inhibit A549/DDP cell proliferation and induce cell apoptosis. Thus, the two drugs appear to have a synergistic effect on apoptosis of A549/DDP cells.

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Cisplatin resistance induced by decreased apoptotic activity in non‐small‐cell lung cancer cell lines

Cited by 37 publications

References 6 publications

Dasatinib promotes paclitaxel-induced necroptosis in lung adenocarcinoma with phosphorylated caspase-8 by c-Src

Dasatinib promotes paclitaxel-induced necroptosis in lung adenocarcinoma with phosphorylated caspase-8 by c-Src

ZNF32 contributes to the induction of multidrug resistance by regulating TGF-β receptor 2 signaling in lung adenocarcinoma

Role of gambogic acid and NaI131 in A549/DDP cells

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