Resveratrol enhances ionizing radiation-induced premature senescence in lung cancer cells.
Resveratrol enhances ionizing radiation-induced premature senescence in lung cancer cells.
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DOI：
10.3892/ijo.2013.2141
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发表时间：
2013-12
影响因子：
5.2
通讯作者：
Wang GY
中科院分区：
文献类型：
--
作者：
Luo H;Wang L;Schulte BA;Yang A;Tang S;Wang GY
在癌症治疗过程中，放射疗法用于> 50%的患者，既作为治愈方式，也用于缓解。然而，放射抗性是放射治疗成功的主要障碍，并且显著地导致肿瘤复发和治疗失败，突出了开发可用于克服肿瘤放射抗性的新型放射增敏剂的需要，从而提高放射治疗的功效。研究表明，白藜芦醇（RV）可使肿瘤细胞对化疗和电离辐射（IR）敏感。然而，RV增加癌细胞辐射敏感性的机制尚未得到很好的表征。在这里，我们表明，RV治疗增强IR诱导的非小细胞肺癌（NSCLC）细胞的细胞杀伤通过一种非肿瘤依赖性机制。进一步的研究显示，与单独用IR或RV处理的细胞相比，在IR与RV组合处理的细胞中，衰老相关的β-半乳糖苷酶（SA-β-gal）阳性衰老细胞的百分比显著更高，这表明RV处理增强了IR诱导的肺癌细胞的过早衰老。彗星试验表明，RV和IR联合治疗导致更多的DNA双链断裂（DSB）比IR或RV单独治疗。DCF-DA染色和流式细胞术分析表明，RV和IR联合治疗导致照射的NSCLC细胞中ROS产生显著增加。此外，我们的研究表明，通过N-乙酰半胱氨酸抑制ROS的产生减弱RV诱导的肺癌细胞的放射增敏作用。总的来说，这些结果表明，RV诱导的放射增敏与照射的NSCLC细胞中ROS产生、DNA-DSB和衰老诱导的显著增加相关，表明RV治疗可能通过增强IR诱导的过早衰老而使肺癌细胞对放射治疗敏感。
Radiotherapy is used in >50% of patients during the course of cancer treatment both as a curative modality and for palliation. However, radioresistance is a major obstacle to the success of radiation therapy and contributes significantly to tumor recurrence and treatment failure, highlighting the need for the development of novel radiosensitizers that can be used to overcome tumor radioresistance and, thus, improve the efficacy of radiotherapy. Previous studies indicated that resveratrol (RV) may sensitize tumor cells to chemotherapy and ionizing radiation (IR). However, the mechanisms by which RV increases the radiation sensitivity of cancer cells have not been well characterized. Here, we show that RV treatment enhances IR-induced cell killing in non-small cell lung cancer (NSCLC) cells through an apoptosis-independent mechanism. Further studies revealed that the percentage of senescence-associated β-galactosidase (SA-β-gal)-positive senescent cells was markedly higher in cells treated with IR in combination with RV compared with cells treated either with IR or RV alone, suggesting that RV treatment enhances IR-induced premature senescence in lung cancer cells. Comet assays demonstrate that RV and IR combined treatment causes more DNA double-strand breaks (DSBs) than IR or RV treatment alone. DCF-DA staining and flow cytometric analyses demonstrate that RV and IR combined treatment leads to a significant increase in ROS production in irradiated NSCLC cells. Furthermore, our investigation show that inhibition of ROS production by N-acetyl-cysteine attenuates RV-induced radiosensitization in lung cancer cells. Collectively, these results demonstrate that RV-induced radiosensitization is associated with significant increase of ROS production, DNA-DSBs and senescence induction in irradiated NSCLC cells, suggesting that RV treatment may sensitize lung cancer cells to radiotherapy via enhancing IR-induced premature senescence.
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DOI：
10.1186/1748-717x-6-144
发表时间：
2011-10-26
期刊：
Radiation oncology (London, England)
影响因子：
--
作者：
Rashid A;Liu C;Sanli T;Tsiani E;Singh G;Bristow RG;Dayes I;Lukka H;Wright J;Tsakiridis T
通讯作者：
Tsakiridis T
影响因子：
6.4
作者：
Sale, S;Tunstall, RG;Gescher, AJ
通讯作者：
Gescher, AJ
DOI：
10.1111/j.1749-6632.2010.05853.x
发表时间：
2011-01-01
期刊：
RESVERATROL AND HEALTH
影响因子：
--
作者：
Patel, Ketan R.;Scott, Edwina;Brown, Karen
通讯作者：
Brown, Karen
影响因子：
5.2
作者：
Gupta SC;Kannappan R;Reuter S;Kim JH;Aggarwal BB
通讯作者：
Aggarwal BB
影响因子：
21.3
作者：
Guo, Xuecui;Keyes, William M.;Papazoglu, Cristian;Zuber, Johannes;Li, Wangzhi;Lowe, Scott W.;Vogel, Hannes;Mills, Alea A.
通讯作者：
Mills, Alea A.