| Lung cancer is one of the most common malignant tumors in our country, nowadays the incidence, mortality rate increased year by year, and younger trend, a serious threat to human life and health, has become one of the major public health problems in the world. Because lung cancer early clinical symptoms are easy to be neglected, resulting in many patients with lung cancer diagnosis has to late, lost the chance operation treatment, only to conservative treatment, and application of surgical treatment after complete resection of the primary lesion, there are still certain tumor recurrence. Nowadays, chemotherapy is still the main treatment of lung cancer, and it also has a certain value for postoperative patients.Currently, platinum is the foundation of small cell lung cancer chemotherapy scheme, and its combined chemotherapy drugs such as paclitaxel, gemcitabine is advanced non-small cell lung cancer with standard first-line chemotherapy regimens. All trans retinoic acid(all- trans retinoic acid, ATRA) is A type of vitamin A acid derivative product, has the effect such as regulating cell proliferation, differentiation, apoptosis, including induction of cell differentiation strongest, it is for use in acute promyelocytic leukemia(acute promyelocytic leukemia, APL) in clinical effect is satisfactory, the clinical remission rate can reach more than 85%; In other experimental study in solid tumors, such as in gastric cancer, breast cancer, and pancreatic cancer studies have confirmed that all trans retinoic acid the potential applied to the treatment of solid tumors.Apoptosis in tumor occurrence, development and outcome of both play an important role. Induce the apoptosis of tumor cell therapy is the hot field of tumor treatment. Survivin gene as new members of the family of apoptosis inhibiting gene, for a variety of tumor tissues and cells increased, due to its specific expression in tumor tissues and plays an important part in antiapoptotic and regulating cell division, survivin increasingly in-depth in cancer research. Cysteine aspartic acid protein 3(caspase- 3) is the key enzyme of mammalian cell apoptosis, it in the form of inactive enzymes original exists in cytoplasm, when activated cell apoptosis.In recent years, the study found, all trans retinoic acid can induce many kinds of solid tumor cell apoptosis, but its mechanism is not fully understood. In this study, we take the effect of ATRA on A549 cells in nude mice bearing Lewis lung cancer, apoptosis was detected in the tumor tissues related gene survivin and caspase-3 messenger RNA(messenger RNA, m RNA) expression changes, to explore mechanisms of ATRA induced apoptosis of lung cancer A549 cells. To provide the theoretical basis for the new treatment of lung cancer. Purpose:Through the animal experiment, to explore the all trans retinoic acid(ATRA) could be induced apoptosis of lung cancer A549 cells in nude mice. Methods:1. The first culture of human lung adenocarcinoma A549 cells in logarithmic growth phase, the collection of human lung adenocarcinoma A549 cells, and the collection of human lung adenocarcinoma A549 cells were subcutaneously injected into nude mice, animal lung adenocarcinoma A549 cell transplantation tumor model of nude mice. The animal model of tumor bearing nude mice were randomly divided into model control group, ATRA group, cisplatin group and cisplatin group, ATRA+ 4 group, 7 rats in each group, were administered 6 times, to calculate the tumor bearing nude mice transplantation tumor volume, body weight and the tumor inhibition rate. At the time of injection intervention second days mice were killed, remove the xenograft tumor. Preservation of tissue from each group were placed in liquid nitrogen, part of the tumor tissue in 10% Formaldehyde Solution fixed, then were embedded in paraffin and pathology, to test the following。2. Using Nick end labeling in situ terminal deoxynucleotidyl transferase mediated(TUNEL) staining, cell apoptosis was detected in 4 groups of nude mice transplantation tumor tissues。3. Using reverse transcription polymerase chain reaction(RT-PCR) method, the expression level was detected in the tumor tissues of caspase-3 and survivin messenger ribonucleic acid m RNA。 Results:1. ATRA group, cisplatin group and ATRA + cisplatin group transplanted tumors had significantly lower than the model group, weight, statistically significant difference(P < 0.05)。ATRA + cisplatin group transplanted tumors present product, weight was lower than that in group ATRA and cisplatin single-agent, statistically significant difference(P < 0.05)。2.ATRA group, cisplatin group and ATRA + cisplatin group of A549 cells in nude mice transplantation tumor cell apoptosis rate increased significantly in the model group, the difference is statistically significant(P < 0.05); Apoptosis rate of ATRA + cisplatin group was obviously higher than that of ATRA and cisplatin group。3.Model group transplanted tumor tissue in the relative expression of caspase-3 m RNA was 0.143±0.053, significantly lower than that of ATRA group, cisplatin group and combination group, the difference is statistically significant(P < 0.05); ATRA role with cisplatin group relative caspase- 3 m RNA expression in transplanted tumor tissue volume were significantly lower than the combination group, the difference statistically significant(all P < 0.05). Survivin in model group transplanted tumor tissue m RNA expression of relative amount was 0.623±0.125, significantly higher than that of ATRA group, cisplatin group and combination group, difference has statistical significance(P < 0.05); ATRA role with cisplatin group transplanted tumor tissue of Survivin m RNA relative expression were significantly higher than that of combination group, statistically significant difference(all P < 0.05). Conclusion:1.ATRA and cisplatin can inhibit human lung adenocarcinoma A549 cells in nude mice transplantation tumor growth; And ATRA + cisplatin combination group than ATRA) and cisplatin, a single drug to inhibit the action of the nude mouse transplantation tumor growth is more apparent, ATRA and cisplatin can synergistic inhibition of human lung adenocarcinoma A549 cells in nude mice transplantation tumor growth. TUNEL method to detect apoptosis of transplanted tumor tissue found that ATRA and/or apoptosis induced by cisplatin can be increased, and ATRA + cisplatin combination group than single drug induced apoptosis effect is stronger, ATRA and cisplatin, promote cell apoptosis occurred in transplanted tumor tissue。2.ATRA can induce apoptosis of tumor bearing nude mice lung adenocarcinoma A549 cells induced expression, and its mechanism may be related to the up regulation of Caspase-3 m RNA and down-regulation of Survivin m RNA expression... |
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