| Background: The incidence and mortality of lung cancer accounted for the first malignant tumor in the large and medium-sized city of the world,its existing treatment includes surgery,radiotherapy,chemotherapy and targeted therapy etc.don't have satisfactory efficacy.There is no larger breakthrough of the patient's symptom improvement and survival time.Traditional Chinese medicine as traditional medicine has a long history in our country,numerous studies have shown that treatment of tumor with traditional Chinese and Western medicine has attenuated synergistic effect.Yiqi Chutan Recipe?YCR?is an effective recipe in the clinical treatment of lung cancer,the previous studies have shown that YCR can effectively inhibit the growth of lung cancer cells and also can inhibit the recurrence and metastasis of lung cancer.Objective:To observe the effects of YCR on expressions of ATF4,CHOP,DR5 and GRP94 of endoplasmic reticulum stress-related protein,to investigate the specific mechanism of spleen deficiency type of lung cancer treated with YCR.Methods: First of all,to build spleen deficiency model mice through the cold diarrhea and irregular diet way.Then lewis lung cancer cells which were in logarithmic growth phase?1×107/m L?were inoculated to the dorsal subcutaneous of the C57BL/6J mice,each mice were inoculated 0.2 m L.48 mice were successful modeled,these lewis lung cancer mice with spleen deficiency were randomly divided into 6 groups,they were model group?normal saline?,chemotherapy group(normal csaline and Cisplatin injection 1mg.kg-1),low dose YCR group(2 g.kg-1),middle dose YCR group(4 g.kg-1),high dose YCR group(8 g.kg-1)and combined medication group(middle dose YCR and Cisplatin injection 1 mg.kg-1),8 mice in each group.During the administration,the mice were observed to measure the body weight and tumor size every 3 days.The mice were killed after 14 days,the tumor weight in mice was measured,the number of lung surface metastases were calculated,the morphological changes of tumor were observed by HE staining method,the expression of ATF4,CHOP,DR5 and GRP94 in tumor tissues was detected by Immunohistochemical method,Western blot method and q RT-PCR method.Results: Compared with the model group,the middle dose group and high dose group could significantly inhibit the growth of tumor,reduce the number of pulmonary metastases,and increase the inhibition rate of lung metastasis?p<0.01 or p<0.05?.compared with the model group,there were massive necrosis tumor cells in the middle dose group,high dose group,chemotherapy group and combined medication group.Compared with the model group,the middle dose group,the high dose group,the chemotherapy group and the combined medication group could significantly increase the expression of endoplasmic reticulum stress protein ATF4,CHOP,DR5,and down-regulate the expression of endoplasmic reticulum molecular chaperone GRP94,among all the groups,the effect of combined medication group was best?P<0.01?.Compared with the chemotherapy group,the tumor size and tumor weight of the combined group were significantly decreased?P<0.05?,the number of lung metastatic nodules were decreased,but there is no significant difference?P>0.05?;the expression of ATF4,CHOP,DR5 in the combined group was significantly higher?p<0.05 or p<0.01?,the expression of GRP94 was significantly lower?p<0.01?.Conclusion: YCR and chemotherapy have different degrees of inhibition on lung cancer,the combined use of the two drugs can obviously improve the curative effect.The mechanism may be related to up-regulating the expression of ATF4,CHOP and DR5 in endoplasmic reticulum stress-related proteins,and down-regulating the expression of GRP94 in endoplasmic reticulum stress-related protein,and to reverse the mechanism of self protection of tumor cells to promote apoptosis of tumor cells. |
PDF Full Text Request