Experimental Study Of The Adverse Psychological Stress Influence The Occurrence And Development Of Human Ovarian Cancer Tumor In Nude Mice By EGFR And Its Downstream Signal Pathway

Background and Objective :The ovarian cancer is one kind of common female reproductive organs malignant tumor,and cervical carcinoma, endometrial cancer merger said female genital three big malignant tumor. Because of ovarian pelvic hiding, the majority of ovarian cancer patients have to advanced disease in asymptomatic are diagnosed, and ovarian cancer is easy to transfer, easy to be widely disseminated, prone to drug resistance and other characteristics of the chemotherapy drugs, make its mortality is high, rank first in gynecological malignant tumor. In recent years, because the conversion of medical model,the connection between psychology and tumor,psychological intervention used in the study of cancer treatment has gradually become the focus of attention of medical research institute.Through to analyze the existing literature reports, the psychological stress play a key role in the development process of ovarian cancer, its inner mechanism is not entirely clear. Early studies suggest that abnormal activation of EGFR and its downstream signal pathway can promote tumor cell proliferation, tumor angiogenesis, tumor metastasis and decrease the apoptosis of tumor cells, the relationship with the germination and development of ovarian cancer is closely, in which the PI3K/AKT pathway and Ras/Raf/MEK/ERK pathway is downstream of EGFR two main signaling pathway. So far,about adverse psychological stress can promote the activation of ovarian cancer closely related signaling pathway, and through the activation of these pathways to promote the development of tumors related research at home and abroad is not reported. This research tries to establish the model of subcutaneous human ovarian carcinoma xenografts in nude mice, to investigate whether the adverse psychological stress through EGFR and its downstream signaling pathways influence human ovarian cancer tumor occurrence, development, and provides a new idea for the psychological treatment and molecular targeted therapy of ovarian cancer.Research Methods:The purchase of rats aged 4 ~ 6 week old female BALB/C(nu/nu) in nude mice,weighing, were randomly divided into two groups, 12 rats in each group. A group:tumor bearing group, subcutaneous transplantation tumor of human ovarian cancer tissue block, do not give stress. B group: tumor bearing + stress group, subcutaneous transplantation tumor of human ovarian cancer tissue block, giving stress.Constructing the model of adverse psychological stress bearing human ovarian cancer xenografts in nude mice. Regularly observed the survival of the state in nude mice and subcutaneously tumor growth in nude mice, measuring the longest diameter of tumor nodules(a) and shortest path of tumor nodules(b), depicting the tumor growth curve diagram. At the the second day after the end of the stress, all the mice were sacrificed(A group, B group), stripping tumor weighing, comparison of A, B two groups of nude mice survival status, body weight,the volume and weight of hypodermic transplant tumor, By immunohistochemical staining, Western blot experimental method for detection of A, B two groups of subcutaneous transplantation tumor tissues of EGFR, AKT/ρ-AKT, ERK/ρ-ERK, VEGF protein expression.Results:1 、 The successful construction of adverse psychological stress model of subcutaneous human ovarian carcinoma xenografts in nude mice.2、The effects of adverse psychological stress on ovarian cancer in nude mice survival status, weight,the volume and weight of hypodermic transplant tumor:(1) Compared with the group in nude mice bearing tumor, tumor bearing + stress group nude mice diet, activities, poor mental state is poor.(2) The tumor bearing group after the experiment nude mice body weight was increased significantly than that before the experiment(P < 0.01),tumor bearing +stress group after the experiment nude mice body weight decreased. After the experiment,the nude mice body weight of tumor bearing + stress group was clearly lower than in tumor group(P < 0.01).(3) After the experiment the volume of subcutaneous transplantation tumor in tumor bearing + stress group was significantly greater than in tumor bearing group(P< 0.01),the growth speed of subcutaneous transplantation tumor in tumor bearing +stress group was significantly greater than in tumor bearing group.(4)After the experiment,the weight of hypodermic transplant tumor in tumor bearing + stress group was clearly heavier than in tumor bearing group(P < 0.01), the growth speed of subcutaneous transplantation tumor in tumor bearing + stress group was significantly greater than in tumor bearing group.3、Using immunohistochemical staining method to detect protein expression of EGFR, AKT/ρ-AKT, ERK/ρ-ERK, VEGF in tumor bearing group and tumor bearing+ stress group: tumor bearing+ stress group subcutaneous transplantation tumor tissue in paraffin sections of EGFR, AKT/ρ-AKT, ERK/ρ-ERK, VEGF protein immunohistochemical score was higher than in tumor bearing group(P < 0.05),VEGF expression difference is most remarkable(P < 0.01).4、The western blot detection of tumor group and tumor + stress group in EGFR,AKT/ρ-AKT, ERK/ρ-ERK, VEGF protein expression:the protein expression of EGFR, AKT/ρ-AKT, ERK/ρ-ERK, VEGF in tumor bearing+ stress group subcutaneous transplantation tumor tissue was increased significantly than in tumor bearing group(P<0.01).Conclusions:Adverse psychological stress may promote the occurrence and development of human ovarian cancer tumor in nude mice by EGFR and its downstream signal pathway.