Relationship Between Expression Of NF-κB And Multidrug Drug Resistance In Gastric Carcinoma Tissue Ang Lymph Node Metastases

Objective: The gastric cancer poses a severe threat to human health. The gastric carcinoma is one of the most common malignant tumors in our country. The soakage, transfer and recrudescence are not only the important reasons of death but also the main factor effect the clinic therapy and prognostic. Up to now,surgery is the main method, but most of patients,who had already undergone radical surgery and chemo-therapy,still have poor prognosis because of the tumor's metastasis and recurrence. The rational chemotherapy helped to improve the curative effect and survival rate on patients with gastric cancer. However,its effect was still not satisfied. By examined the sensitivity of anti-cancer drug on gastric cancer,multidrug resistance (MDR) presents an important obstacle for the success of the treatment. The MDR describes the cross-resistance of tumor cell lines to several structurally unrelated chemotherapeutic agents after exposure to a single cytotoxic drug. Apoptosis is a process of self destruction that requires the activation of a genetic programme that may lead to the changes in cell morphology, the fragmentation of DNA, and the protein cross linking. Less apoptosis may lead to carcinogenesis. Mechanism of MDR of tumor cells is unusual complicate, it is related to various factors and processes, and more and more researchers focus on it. Many aspects were involved in the molecular-mechanisms of drug resistance which including different expression of oncogene and antioncogene. The changes of DNA damaged and repaired the abnormal expression of multidrug associated protein and so on. Since MDR is one of the main obstacles to successful chemotherapy of cancer, the extensive investigation has been made to understand the resistance mechanism and to develop the strategies to reverse the resistance. NF-κB is a kind of nuclear transcription protein that exist in all cells of the body. It took part in the regulation of inflammation, immunity and stress. Recently, it has been proved to play an important role in cell proliferation, apoptosis, cytokine production, and the activation of oncogenesis. It can propel the progress of cellular cycle, and inhibit the sequential apoptosis of cells, through monitoring transcript of the related genes, thus affect their cancelations course. It has been suggested that NF-κB plays an important regulative role in the invasion and metastasis of gastric carcinoma and that its activation may be correlated with the carcinogenesis, invasion and metastasis of tumor, which is becoming a hot spot of tumor research. Recent study indicated that the chemotherapeutic drugs can activate NF-κB when they come into effect. NF-κB is a kind of transcription factor that exists extensively,act diversely and is related to the immunity react, apoptosis,inflammation injury,etc. So, it is related to MDR.In this study, we detect the gene and protein expression of NF-κB ,MDR1/ P-gp and Bcl-2/Bax in the gastric cancer. what is on the expression of the gastric carcinoma tissues, metastatic lymph node tissues NF-кB, MDR1/ P-gp and Bcl-2/Bax correlation research. Therefore, in this study we detected the expressions of NF-кB, MDR1/ P-gp and Bcl-2/Bax in gastric carcinoma issues, and metastatic lymph node tissues by S-P immunohisto-chemistry technique or RT-PCR method, analyzed the relationship between the expressions and the ability of invasion,the metastasis of tumor cells, the expressions and the biological behavior of gastric carcinoma. The OD values were detected by MTT method and the CI values of 5 kinds of chemotherapy were calculated according to the formula. This article aims at the relationship between the expression of NF-кB and the related factors of MDR.Methods:In this article, we select 66 samples of gastric carcinoma. All patients had gastrectomy in the 4th hospital of HeBei Medical University from February 2008 to August 2008. We gathered gastric carcinoma and metastatic lymph node (confirmed by patho) of every patient. The new method that to make tissue array by microarray technology. We detect the gene and protein expression of NF-κB ,MDR1/ P-gp and Bcl-2/Bax in gastric carcinoma tissues, and metastatic lymph node tissues by S-P immunohisto chemical technique or RT-PCR method. The OD values were detected by MTT method and the CI values of 5 kinds of chemotherapy were calculated according to the formula. This article aims at the relationship between the expression of NF-кB and the related factors of MDR. All of statistical analyses were carried out with SPSS 12.0 and P<0.05 were considered significant.Results:1.The results of NF-кB p65 and the related factors of MDR mRNA expression in two different gastric cancer tissues.The mRNA expressions of NF-кB p65, P-gp, Bcl-2 were higher in LNMs (lymph node metastases)than in PT(primary tumor)(all P<0.05), but Bax mRNA was lower in LNMs(P<0.05). There was positive correlativity of NF-кB p65 mRNA between PT and LNMs(P<0.05). In PT, there was positive correlativity between NF-кB p65 and MDR1 (P<0.01), and the negative correlativity was found between NF-кB p65 and Bax, Bcl-2 and Bax(both P<0.05). There was no statistical correlativity among these factors in LNMs.2. The results of NF-кB p65 and the related factors of MDR protein expression in two different gastric cancer tissues.The protein expressions of NF-кB p65, P-gp, Bax were higher in LNMs and in PT(all P<0.05).There was no statistical correlativity of Bcl-2 between PT and LNMs(P>0.05);There was positive correlativity of P-gp and Bax in PT and LNMs.There was no statistical correlativity of NF-кB p65 between PT and LNMs(P>0.05); In PT there was positive correlativity between NF-кB p65 and P-gp (P<0.01), and the negative correlativity was found between NF-кB p65 and Bax, Bcl-2 and Bax(both P<0.05). There was no statistical correlativity among these factors in LNMs.3. Relationship between Expression of 5 kinds of chemotherapy and Chemo- sensitivities in Gastrointestinal Carcinomas.The inhibition rates of LNMs cells for VCR were lower than those of PT (all P<0.05), There was no statistical correlativity of 5-FU,PTX,OXA,eADM between PT and LNMs(P>0.05);4.Relationship between Expression of NF-кB p65,multidurg resistance associated factors and Chemosensitivities in Gastrointestinal Carcinomas. In PT, the inhibition rates to 5-FU and PTX were significantly much lower in the NF-кB p65 strong expression group than the weak group (P<0.05). The inhibition rates for 5-FU,PTX and OXA in P-gp strong expression group were lower than those in weak group (all P<0.05). There were the lower inhibition rates for 5-FU,PTX and eADM in Bcl-2 strong expression group (all P<0.05).The inhibition rates for 5-FU,OXA and eADM in P-gp strong expression group were higher than those in weak group (all P<0.05).In LNMs the inhibition rates to 5-FU was significantly much lower in the NF-кB p65 strong expression group than the weak group (P<0.05). The inhibition rates for 5-FU,PTX and OXA in P-gp strong expression group were lower than those in weak group (all P<0.05). There were the lower inhibition rates for 5-FU and PTX in Bcl-2 strong expression group (all P<0.05).The inhibition rates for 5-FU,OXA and eADM in P-gp strong expression group were higher than those in weak group (all P<0.05).Conclusion:1. The mRNA expressions of NF-кB p65, P-gp, Bcl-2 were higher in LNMs than in PT. NF-кB p65, P-gp and Bcl-2 were considered to have participated natural MDR in gastrointestinal carcinomas . NF-кB relate to MDR1/P-gp in gastrointestinal carcinomas , but NF-кB didn't only control iter of MDR1. The pathway of apoptosis control was so. NF-кB was considered to have participated MDR in gastrointestinal carcinomas .2. The protein expressions of NF-кB p65, P-gp, Bcl-2 were higher in LNMs than in PT. NF-кB p65, P-gp and Bcl-2 were considered to have participated natural MDR in gastrointestinal carcinomas . NF-кB p65 relate to MDR1/P-gp in gastrointestinal carcinomas , but NF-кB p65 didn't only control iter of MDR1. The pathway of apoptosis control was so. NF-кB p65 was considered to have participated MDR in gastrointestinal carcinomas. 3. Heterogeneity of chemosensitivity to antitumor drugs was shown in metastatic lymph nodes in gastric cancers. Heterogeneity of chemosensitivity was higher in LNMs than in PT. The chemosensitivity of gastrointestinal cancer primary tumor in the histoculture drugs response assay may not give a good indication of the chemosensitivity in metastatic lesions.4. The over-expression of MDR-related factors in gastrointestinal carcinomas was associated with the chemosensitivity of some drugs, but not all.In a word,Heterogeneity of chemosensitivity to antitumor drugs is shown by metastatic lymph nodes in gastric cancers. The chemosensitivity of gastric carcinoma primary tumor in the histoculture drugs response assay may not give a good indication of the chemosensitivity in metastatic lesions. The NF-кB takes part in MDR of gastric carcinoma. The LNMs of gastric carcinoma are heterogeneous with respect to expression of NF-кB and response to chemo-sensitivities. The accurate chemosensitivities was regulated by the multifactor and mechanisms. The MDR related factors did not play responsible role as specific and accurate predictors for the clinical chemosensitivity, which was regulated by the multifactors and mechanisms. The over-expression of MDR-related factors in gastric carcinoma was associated with the chemo-sensitivities of only a part of drugs.