Luo Shuchun, Bai Yifeng, Lan Haitao
Department of Oncology, Sichuan Provincial People's Hospital, Chengdu 610000, China.
Department of Oncology, Sichuan Provincial People's Hospital, Chengdu 610000, China. Email:
Zhonghua Zhong Liu Za Zhi. 2014 Oct;36(10):733-8.
To investigate the role of wild-type p53-induced gene 1 (WIG-1) on the regulation of multi-drug resistance in small cell lung cancer.
The expressions of WIG-1 protein and gene were detected by Western blot and real-time PCR (RT-PCR) in both the drug-sensitive H69 and drug-resistant H69AR cell lines, respectively. Meanwhile, the differential expression of WIG-1 was also detected in peripheral blood samples of responders and non-responder patients. Furthermore, the WIG-1 expression was inhibited by siRNA in H69AR cells, then the drug-sensitivities of H69AR cells to chemotherapy agents such as ADM, DDP, VP-16 were detected by CCK8 assay, and apoptosis rate was detected by flow cytometry. The possible association of WIG-1 with clinical parameters was evaluated.
The expression of WIG-1 was significantly increased in H69AR cells (5.965 ± 0.890) than that in the H69 cells (1.023 ± 0.127) (P = 0.007). The expression of WIG-1 was significantly increased in the non-responder patients (4.169 ± 0. 970) than in the H69 cells and responders (1.673 ± 0.127) (P < 0.001). The drug-sensitivities of H69AR cells to chemotherapeutic drugs were increased when the expression of the WIG-1 was down-regulated. The apoptosis rate was significantly decreased in the H69AR cells (1.037 ± 0.049)% compared with that in the H69 cells [(7.963 ± 0.097)%, (P < 0.01)]. The apoptosis rate was increased in the H69AR-Si-WIG-1 cells (20.915 ± 0.890)% than that of (1.037 ± 0.049)% in the H69AR and H69AR-NC group (2.025 ± 0.097)% (P < 0.01). The expression of WIG-1 was not significantly associated with gender, and age (P > 0.05), but significantly correlated with chemosensitivity, overall survival and clinical stage (P < 0.001 for all).
Our results suggest that WIG-1 is involved in the regulation of the multidrug resistance mechanism in small cell lung cancer. Selective silencing of the WIG-1 gene may reverse the multidrug resistance of SCLC via increasing cell apoptosis.
探讨野生型p53诱导基因1（WIG-1）在小细胞肺癌多药耐药调控中的作用。
分别采用蛋白质免疫印迹法（Western blot）和实时荧光定量聚合酶链反应（RT-PCR）检测药敏H69和耐药H69AR细胞系中WIG-1蛋白和基因的表达。同时，检测应答者和非应答者患者外周血样本中WIG-1的差异表达。此外，通过小干扰RNA（siRNA）抑制H69AR细胞中WIG-1的表达，然后采用细胞计数试剂盒（CCK8）法检测H69AR细胞对阿霉素（ADM）、顺铂（DDP）、依托泊苷（VP-16）等化疗药物的敏感性，采用流式细胞术检测细胞凋亡率。评估WIG-1与临床参数之间的可能关联。
H69AR细胞中WIG-1的表达（5.965±0.890）明显高于H69细胞（1.023±0.127）（P = 0.007）。非应答者患者中WIG-1的表达（4.169±0.970）明显高于H69细胞及应答者（1.673±0.127）（P < 0.001）。下调WIG-1表达后，H69AR细胞对化疗药物的敏感性增加。与H69细胞相比，H69AR细胞的凋亡率显著降低[（7.963±0.097）%比（1.037±0.049）%，（P < 0.01）]。H69AR-Si-WIG-1细胞的凋亡率（20.915±0.890）%高于H69AR和H69AR-NC组的（1.037±0.049）%及（2.025±0.097）%（P < 0.01）。WIG-1的表达与性别、年龄无显著相关性（P > 0.05），但与化疗敏感性、总生存期和临床分期显著相关（均P < 0.001）。
我们的结果表明，WIG-1参与小细胞肺癌多药耐药机制的调控。选择性沉默WIG-1基因可能通过增加细胞凋亡来逆转小细胞肺癌的多药耐药性。
