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Effect of Chlorin e6/SDT and Paclitaxel on the Proliferation of Human Lung Adenocarcinoma Cell SPCA-1

Author: ZhengRuiNian
Tutor: ZhangWeiMin；WangXiaoHuai
School: Southern Medical University,
Course: Oncology
Keywords: SDT Chlorin e6 Lung tumor - monocytes Cell proliferation Taxol Lung tumors
CLC: R734.2
Type: Master's thesis
Year: 2010
Downloads: 57
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Abstract

Lung cancer is the number one killer of the tumor in the threat to human life and health, 70% of patients at the time of diagnosis is locally advanced or distant metastasis. The third generation chemotherapy drugs and platinum combination chemotherapy is the standard first-line treatment of advanced non-small cell lung cancer (NSCLC) Problems efficacy to reach the platform: efficiency of 25% to 35%, the median survival of 8 to 10 months . To the epidermal growth factor receptor (EGFR) and its cellular signal transduction as a target for lung cancer targeted therapy adverse reactions, but its effectiveness with EGFR gene mutations, low rate of the general population, and the median resistance time 6-10 months. Chemotherapy and anti-angiogenesis targeted drug combination therapy also prolonged survival only 1-3 months. Therefore, the search for efficiency, low toxicity of the new method for the treatment of lung cancer, the important issues facing the medical profession. SDT (Sonodynamic therapy, SDT) is a tumor in the treatment of new ideas, new methods developed on the basis of photodynamic therapy (Photodynamic therapy, PDT). By ultrasonic focus on specific parts of the tumor, chemical activation and tumor affinity sonosensitizer molecules, the generation of reactive oxygen free radicals, which kill tumor cells in a targeted manner. Ultrasonic and penetrating power than the red selective focus, and on the surrounding normal tissue with less damage, Therefore, the anti-tumor effect of SDT has a good prospect. View of the majority of the photosensitizer with sonodynamic role, sonodynamic multi photosensitizer say anything sensitizer sonodynamic treatment, there are two problems: First, the photosensitizer tumor-specific aggregation of low, normal tissue to clear slow and light toxicity Higher shortcomings limit the SDT was approved for clinical use, and therefore need to develop new sonosensitizer; SDT how to further improve the efficacy in combination with other treatment. Chlorin e6 (Chlorin e6) is a structure similar to the hematoporphyrin chlorophyll degradation products. Yamamoto, T, for the first time in 1974 by laser irradiation a Chlorin e6 photodynamic therapy Ehrlich cell tumor killing effect is obvious. After photodynamic anti-tumor effect was confirmed by a large number of animal experiments, and possessed low toxicity, tumor-specific aggregation the normal tissues Clear, low phototoxic side effects, is an attractive prospect photosensitizer, Chlorin e6 completed duration of clinical trials of photodynamic therapy of melanoma skin metastases. In view of the that the majority the photosensitizer with sonodynamic role, the aim of this study is to role by observing Chlorin e6 combined with ultrasound on human lung adenocarcinoma SPCA-1 cell growth clear whether with sonosensitizer sonodynamic. Advanced NSCLC, first-line therapy to systemic chemotherapy, Taxol (Paclitaxel) is the third generation of the first-line treatment of advanced NSCLC chemotherapy drug, and has confirmed its view of the past a lot of pre-clinical and clinical studies with radiosensitization effect and photodynamic sensitizing effect The second purpose of this study is to explore the inhibition of human lung adenocarcinoma SPCA-1 cell growth with the sensitizing effect of paclitaxel on Chlorin e6 sonodynamic. The first part Chlorin e6 sonodynamic Chlorin e6 sonodynamic human lung adenocarcinoma cell SPCA-1 Growth of purpose: To observe the human lung adenocarcinoma cell SPCA-1 acute cytotoxicity. Methods: four MTT (3 - [4,5-dimethylthiazol-2-yl] -2, 5-diphenyl-tetrazolium bromide, MTT) color spectrophotometric detection the pure ultrasound harmony sensitizer dihydrogen porphine e6 (Chlorin e6, E6) SPCA-1 and normal human peripheral blood mononuclear cells (normal peripheral mononuclear cell, PMNC) cytotoxicity, and in order to determine the sound according to parameters (1.0W/cm2 × 60s) and Chlorin e6 dose (0.05 mg / mL ~ 0.2 mg / mL), observe sound Chlorine6 dynamic effects of acute killing effect of the SPCA-1 the cells and PMNC cells, cell morphology was observed inverted microscope. Experimental results are presented as mean ± standard deviation (Mean ± SD) said, The SPSS13.0 software related data for analysis, the t-test was used to compare between the two groups; compared using one-way ANOVA analysis of variance between groups, and then different groups were compared using LSD test, P lt; 0.05 determines significant difference. Results: ultrasound and Chlorine e6 cell growth 1.0 MHz ultrasound (1.0-2.0) W/cm2 60s was intensity dependent inhibition of the SPCA-1 and PMNC cell growth inhibition ultrasound 50% SPCA-1, and PMNC cell growth the intensity were: 1.45 W/cm2, 1.44 W/cm2 was no significant difference (t = 0.185, P = 0.857). Chlorine e6 (0.4 ~ 3.2) mg / mL in a concentration-dependently inhibited the growth of SPCA-1 and PMNC cells. Chlorine e6 inhibit the SPCA-1 and PMNC cell growth IC50 values ??were: 0.79 mg / mL, 0.97 mg / mL, no statistically significant difference (t = -1.611, P = 0.138). 2, the combined effects on cell growth ultrasound Chlorine e6 the 1.0 W/cm2 simple ultrasound SPCA-1 and PMNC cell viability were 79.6%, 78.0%, compared with the normal control group were statistically significant (P lt; 0.05), the SPCA-1 and PMNC cells showed no significant difference (t = 0.419, P = 0.684). Three different concentration of 0.05 mg / mL, 0.1 mg / mL and 0.2 mg / mL Chlorine e6 pure role SPCA-1 and PMNC cell growth had no significant role (P gt; 0.05); 1.0 W/cm2 ultrasound combined the three Chlorine e6 effect of different concentrations of SPCA-1 cell viability were 66.3%, 52.9% and 28.3%, PMNC cell survival rates were 78.8%, 80.4% and 75.3%. Compared with the pure ultrasound and Chlorinee6, ultrasound combined Chlorine e6 SPCA-1 cell growth inhibition of a statistically significant difference (P lt; 0.05), no significant differences (P gt the PMNC cell viability; 0.05). 3 inverted microscope ultrasound Chlorine e6 separate and combined effects SPCA-1 cells survived high magnification, round, translucent, membrane integrity, abundant cytoplasm of cells as living cells; multiforme, not translucent. membrane rupture, the cytoplasm of the loss of the cells as dead cells. Group C, the U1.0 group, E0.2 group U1.0E0.2 group SPCA-1 cell mortality were 1.6%, 21.5%, 2.3%, and 69.8%, respectively. Joint with pure 1.0 W/cm2 the ultrasound the U1.0 group and simply 0.2 mg / mL Chlorine e6 E0.2 ratio, ultrasonic Chlorine e6 U1.0E0.2 SPCA-1 cell mortality was significantly higher (P lt ; 0.05). Conclusion: Ultrasound combined chlorin e6 sonodynamic can acute anti-human lung adenocarcinoma SPCA-1 cells possessed specificity, Chlorine e6 is expected to become a new sonosensitizer for sonodynamic the treatment of non-small cell lung cancer. The second part of paclitaxel of Chlorin e6 sonodynamic inhibition of human lung adenocarcinoma SPCA-1 cell growth sensitizing effect of purpose: to observe Chlorin e6 sonodynamic on human lung adenocarcinoma long SPCA-1 cell growth inhibition and observation paclitaxel Chlorin The e6 sonodynamic inhibition of human lung adenocarcinoma SPCA-1 cell growth, and aims to explore paclitaxel on the chlorin e6 sonodynamic whether with sensitizing effect. Methods: MTT (MTT) color pure ultrasound spectrophotometric detection, sonosensitizer Chlorin e6 and paclitaxel SPCA-1 cytotoxicity, and in order to determine the sound according to the parameters (1.0W/cm2 × 60s), Chlorin e6 dose (0.025 mg / mL) and paclitaxel dose (1 × 10-7M) observed Chlorine6 sonodynamic inhibition of human lung adenocarcinoma SPCA-1 cells grown long, and observation of paclitaxel on Chlorin e6 The sonodynamic suppression SPCA-1 cell growth impact. The experimental results are presented as mean ± standard deviation (Mean ± SD), The SPSS13.0 software related data for analysis and comparison between groups using one-way ANOVA variance analysis, then LSD test was used to compare between different groups, P lt; 0.05 determine a statistically significant difference. The results: 1, ultrasound, Chlorine e6 and paclitaxel alone SPCA-1 cells grown 1.0 MHz ultrasound at 1.0 W/cm2 to 2.0W/cm2 intensity range role 60s was intensity-dependent inhibition of growth of SPCA-1 cells. Chlorine e6 and paclitaxel respectively in the concentration range of 0.05mg/mL ~ 1.6mg/mL and 1 × 10-9M ~ 1 × 10-6M was concentration-dependently inhibited the growth of SPCA-1 cells. SPCA-1 cells survival of Chlorine e6 sonodynamic of SPCA-1 cell growth impact of 1.0 W/cm2 ultrasound was 78.8%, compared with the normal control group, a statistically significant difference (P lt; 0.05); 0.025mg SPCA-1 cells / mL concentration Chlorine e6 role in the survival rate was 96.0%, compared with the normal control group, no significant difference (P gt; 0.05); 1.0 W/cm2 ultrasound combined 0.025 mg / mL concentration Chlorine e6 role SPCA- 1 cell survival rate was 56.9%, compared with the pure ultrasound and Chlorine e6 ultrasound combined Chlorine e6 sonodynamic SPCA-1 cell growth inhibition was significantly increased (P lt; 0.05). 3, paclitaxel of Chlorine e6 sonodynamic suppression SPCA-1 cell growth of 1.0 W/cm2 ultrasound combined with 0.025 mg / mL concentration Chlorine e6 role SPCA-1 cell survival was 56.9%, compared with the normal control group, statistically difference (P lt; 0.05); concentration of 1 × 10-7M paclitaxel for SPCA-1 cell survival rate was 54.6%, compared with the normal control group, a statistically significant difference (P <0.05); Chlorine the e6 sonodynamic (ultrasound: 1.0 W/cm2; Chlorin e6: 0.025 mg / mL) combined with a concentration of 1 × 10-7M paclitaxel for SPCA-1 cell survival rate was 8.5%, compared with Chlorine e6 sound power and paclitaxel, Chlorine e6 sound power combined with paclitaxel on SPCA -1 inhibition of cell growth was significantly enhanced (P LT; 0.05). Conclusion: Ultrasound combined chlorin e6 sonodynamic can long inhibition of cell growth of human lung adenocarcinoma SPCA-1 and paclitaxel Chlorin e6 sonodynamic inhibit the growth of human lung adenocarcinoma SPCA-1 cells with the sensitizing effect of paclitaxel is expected to become a sensitizing agent used in the sensitizing sonodynamic the treatment of non-small cell lung cancer.

Effect of Chlorin e6/SDT and Paclitaxel on the Proliferation of Human Lung Adenocarcinoma Cell SPCA-1

Abstract

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