本文選題：光動力治療　切入點：順鉑　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:鉑類抗腫瘤藥物是很多實體腫瘤的一線化療藥物,耐藥性的產(chǎn)生是導(dǎo)致腫瘤化療失敗的重要原因。因此,需要一些新的策略來克服順鉑耐藥。光動力療法(Photodynamic therapy,PDT)是一種獲得臨床認(rèn)可的癌癥治療方法,基于光敏劑、光照和氧氣之間的光化學(xué)反應(yīng)。光動力療法分兩個階段完成,先給予光敏劑處理,隨后再用適當(dāng)波長的光照射局部腫瘤激活光敏劑,從而發(fā)揮抗腫瘤效應(yīng)。將多種具有不同毒性作用的治療方法聯(lián)合應(yīng)用,是當(dāng)代腫瘤醫(yī)學(xué)提高治療療效常用的策略。聯(lián)合治療時,由一種治療方法誘導(dǎo)的抗性有可能會被另一種方法克服。目的:本文將探討光敏劑焦脫鎂葉綠酸甲酯介導(dǎo)的光動力治療對順鉑耐藥肺癌細(xì)胞的滅活,及PDT與順鉑(DDP)的聯(lián)合效應(yīng)。方法:采用肺癌細(xì)胞A549及其DDP耐藥株A549/DDP。實驗分為對照組、DDP組、PDT組和PDT+DDP組。對照組不加藥物,DDP組給予14μmol/L DDP處理,PDT組給予2μmol/L MPPa、2.4 J/cm2光照處理,PDT+DDP組聯(lián)合應(yīng)用PDT和DDP。以CCK-8法測定細(xì)胞活性,應(yīng)用Annexin V-FITC/PI雙染檢測細(xì)胞凋亡;2',7'-二氯熒光黃雙乙酸鹽(DCFH-DA)檢測細(xì)胞內(nèi)活性氧(ROS)水平;蛋白印跡法檢測Caspase-3、Bcl-2和Bax蛋白表達(dá)。結(jié)果:PDT在A549和A549/DDP細(xì)胞產(chǎn)生毒性,與對照組相比存活率降低(P0.05);與對照組、DDP組和PDT組相比,在二株細(xì)胞中PDT+DDP組的存活率最低(P0.05),定量分析聯(lián)合指數(shù)分別為1.11、1.10,提示聯(lián)合效應(yīng)均為相加。在二株細(xì)胞中,PDT+DDP組凋亡率和細(xì)胞內(nèi)ROS均高于對照組、DDP組及PDT組(P0.05)。蛋白質(zhì)印跡法檢測發(fā)現(xiàn)在二株細(xì)胞,與對照組相比,PDT組和PDT+DDP組,Caspase-3和Bax蛋白表達(dá)升高,Bcl-2蛋白表達(dá)降低(P0.05)。結(jié)論:PDT或聯(lián)合DDP對耐藥肺癌細(xì)胞具有明顯殺傷效應(yīng),主要通過ROS?線粒體途徑凋亡實現(xiàn);PDT與DDP的聯(lián)用效應(yīng)為相加。
[Abstract]:Background: platinum antitumor drugs are the first-line chemotherapeutic agents in many solid tumors, and the occurrence of drug resistance is an important factor leading to the failure of chemotherapy. New strategies are needed to overcome cisplatin resistance. Photodynamic therapy (PDT) is a clinically recognized cancer treatment based on photochemical reactions between Guang Min, light and oxygen. Photodynamic therapy is done in two phases. First, Guang Min was given, and then local tumor was irradiated with appropriate wavelength of light to activate Guang Min, so as to exert anti-tumor effect. A variety of treatment methods with different toxic effects were used in combination. It is a commonly used strategy in modern oncology medicine to improve the therapeutic effect. Resistance induced by one therapeutic method may be overcome by another. Objective: to investigate the inactivation of cisplatin resistant lung cancer cells induced by photodynamic therapy mediated by methyl pyrodeoxylate, a Guang Min agent, in vitro. Methods: lung cancer cell line A549 and its DDP resistant strain A549 / DDP were divided into control group and PDT DDP group. The control group was treated with 14 渭 mol/L DDP and the control group was given 2 渭 mol/L MPPA 2.4 J/cm2 illumination. PDT and DDP were used in the DDP group. The cell activity was measured by CCK-8 assay. Annexin V-FITC/PI double staining was used to detect the expression of Caspase-3 Bcl-2 and Bax protein in A549 and A549/DDP cells, and DCFH-DA-DCFH-DAA was used to detect the expression of Caspase-3 Bcl-2 and Bax protein in A549 and A549/DDP cells. Compared with the control group, the survival rate was lower than that in the control group, and compared with the control group and the PDT group, the survival rate was lower than that in the control group. The survival rate of PDT DDP group was the lowest, and the quantitative analysis index was 1.111.10, indicating that the combination effect was additive. The apoptosis rate and intracellular ROS of PDT DDP group were higher than those of control group and PDT group. Two cell lines were detected by qualitative blotting. Compared with the control group and PDT DDP group, the expression of Caspase-3 and Bax protein increased and the expression of Bcl-2 protein decreased P0.05.Conclusion the effect of PDT / PDT or combined DDP on drug-resistant lung cancer cells is obvious. Mitochondrial pathway apoptosis can achieve the combined effect of PDT and DDP.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R730.5

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本文編號：1673813