The Experimental Study On Relationship Between Drug Sensitivity Differences Of Lung Cancer Cell In Vitro And Resistance-related Protein

Part Ⅰ The study on the chemosensitivity assay in vitro of theperipheral lymphocytes of patients with lung cancer taking place oftumor cellsObjective: In the pathological type of lung cancer, Non-small cell lungcancer accounts for about80%. Chemotherapy plays an important role in thecomprehensive treatment based on operation of non-small cell lung cancer.But, in the clinical work, patients with the same pathological type often havedifferent sensitivity to the same chemotherapy drugs. In recent years, someliterature have reported that drug sensitivity test of tumor cell in vitro guidedchemotherapy(individualized chemotherapy) was better than conventionalchemotherapy, because individualized chemotherapy could improve thequality of life and the rate of long-term survival of patients. It is not easy tofind lung cancer in the early stage. so when many patients go to hospital, theyhave lost opportunity of operation; For various reasons, we can not obtainenough specimens; Through several chemotherapies, many patients can notget better effect for drug resistance. Because of above-mentioned situations,we can not conduct drug sensitivity test of lung cancer cell in vitro and howcan we conduct individualized chemotherapy? Many researches haveconfirmed that there was a good positive correlation between the tumor cellsof many organs and the peripheral blood lymphocytes to the samechemotherapy drug. However, few researches are about correlation betweendrug sensitivity of lung cancer cells in vitro and their own peripheral bloodlymphocytes. This experiment was about susceptibility test of lung cancercells in vitro and their own peripheral blood lymphocytes, and detected thecorrelation between lung cancer cells and their own peripheral bloodlymphocytes. We investigated whether drug sensitivity of peripheral blood lymphocytes can replace that of the lung cancer cells.Methods: In vitro, we cultured lung cancer cells and its own peripheralblood lymphocytes of60patients with non-small cell lung cancer, who wasnot treated before operation. After48hours, we used MTT method to detectthe drug sensitivity of these cells to CBDCA,5-Fu,CTX and VCR which areusually applied in clinic.Results:1Morphology of cell:The number of tumor cells in experimental group were less than the number oftumor cells in contrast group. Tumor cells in experimental group were looselyarranged and many of them were dead. The number of peripheral bloodlymphocytes in experimental group were less than the number of peripheralblood lymphocytes in contrast group. In experimental group, refraction ofperipheral blood lymphocytes changed worse.2The test of Susceptibility:2.1According to the average rate of inhibition in lung cancer cells by drugs,We could conclude the following facts. Squamous cell carcinoma wassensitive to CBDCA,and5-Fu, but not sensitive to VCR and CTX. However,adenocarcinoma was sensitive to CBDCA, VCR and5-Fu, but not sensitive toCTX.2.2Peripheral blood lymphocytes of patients with lung cancer was sensitive toCBDCA,5-Fu,and VCR, but not sensitive to CTX.2.3There was a good positive correlation between the rate of inhibition to thesame chemotherapeutic drug (CBDCA, VCR,5-Fu and CTX)of Lung cancercells and that of their own peripheral blood lymphocytes. Coefficient ofcorrelation were0.701,0.668,0.543,0.696, which had a statisticalsignificance(P<0.05).2.4According to the rate of sensitivity of lung cancer cells and peripheralblood lymphocytes in60cases to the same Chemotherapy drugs, We couldconclude the following facts.(the rate of sensitivity=the number of cases ofsensitivity/the total number of cases×100%). There was no significant difference between the rate of sensitivity to the same chemotherapeuticdrug(CBDCA, VCR,5-Fu and CTX) of Lung cancer cells and that of theirown peripheral blood lymphocytes. X2were0.786,1.645,0.263,0.261, whichhad no statistical significance(P＞0.05).Conclusions:1Lung cancer cells and peripheral blood lymphocytes of the same patienthave a good positive correlation to the drug sensitivity of the samechemotherapeutic drug.2When lung cancer patients have lost the opportunity of operation or solidtumor specimens can't be obtained due to various reasons, we can use the drugsensitivity of chemotherapeutic drugs for peripheral blood lymphocytes toreplace tumor cells to select drugs.Part Ⅱ The study on the Mechanism of lung cancer cells in vitrosusceptibility differencesObjective: We detected the expression levels of ERCC1,LRP and TP inthe non-small cell lung cancer by the way of immunohistochemistry andanalyzed the correlation between drug sensitivity of lung cancer cells and theexpression levels of resistance-related protein, and discovered the molecularmechanisms of drug sensitivity differences.Methods: We detected60cases of paraffin sections of non-small celllung cancer by the way of immunohistochemistry to discover the expressionlevels of ERCC1,LRP and TP.Results:1The result of immunohistochemical staining1.133cases were positive expression in the expression of ERCC1in60casesof lung cancer. The positive expression rate of ERCC1was55.0%。Thepositive expression rate of squamous cell carcinoma was41.2%(14/34) andthe positive expression rate of adenocarcinoma was73.1%(19/26). Thepositive expression rate of adenocarcinoma was significantly higher than thatof squamous cell carcinoma. The expression of ERCC1was significantly different by statistical tests between squamous cell carcinoma andadenocarcinoma(x2=6.058, P=0.014).1.228cases were positive expression in the expression of LRP in60cases oflung cancer. The positive expression rate of LRP was46.7%(28/60). Thepositive expression rate of squamous cell carcinoma was35.3%(12/34) andthe positive expression rate of adenocarcinoma was61.5%(16/26). Thepositive expression rate of adenocarcinoma was significantly higher than thatof squamous cell carcinoma. The expression of LRP was significantlydifferent between squamous cell carcinoma and adenocarcinoma by statisticaltests(x2=4.077, P=0.043).1.327cases were positive expression in the expression of TP in60cases oflung cancer. The positive expression rate of TP was45.0%。The positiveexpression rate of squamous cell carcinoma was44.1%(15/34) and thepositive expression rate of adenocarcinoma was46.2%(12/26). The positiveexpression rate of adenocarcinoma was higher than that of squamous cellcarcinoma, but the expression of TP was not significantly different bystatistical tests between squamous cell carcinoma and adenocarcinoma(x2=0.025, P=0.875).1.4In the negative expressions of ERCC1, the number of sensitivity toCBDCA was significantly higher than that of the positive expressions ofERCC1, and the result had a statistical significance (P<0.05).1.5In the negative expressions of LRP, the number of sensitivity to CTX wassignificantly higher than that of the positive expressions of LRP. The resulthad a statistical significance (P<0.05).1.6In the positive expressions of TP, the number of sensitivity to5-FU wassignificantly higher than that of the negative expressions of TP. The result hada statistical significance (P<0.05).Conclusions:1The high expression level of ERCC1may be the main factor of lung cancernot sensitive to CBDCA; The high expression level of LRP may be the mainfactor of lung cancer not sensitive to CTX; The high expression level of TP may be the main factor of lung cancer sensitive to5-FU.2The expression level of Resistance-related protein can predict sensitivity tochemotherapy. The expression level of resistance-related protein may be themain factor of lung cancer patients' different drug sensitivities tochemotherapy drugs.