Effect Of Dihydrotestosterone On TNF-α Inhibiting Proliferation Of Prostatic Cancer Cells

Tumor necrosis factor-alpha (TNF-α) can mediate apoptosis or proliferation of a lot of cells. TNF- a has anti-tumor activity in vivo and in vitro, and is effective in treatment of lots kinds of tumors. In USA and Europe, the morbidity of prostate cancer is in the first or the second place in all of the male cancers. The incidence of prostate cancer increases in China in recent years. And now the radical prostatectomy and endocrine therapy are usually used to extirpate the tumor and to block the action of androgen respectively to treat prostate cancer. But prostate cells can syntheses dihydrotestosterone from androgen precursor of adrenal origin. Experiments showed that trace androgen had marked effect on proliferation of prostate cancer cells. But it has not reported whether the trace androgen influences the action of TNF- a inhibiting proliferation of prostate cancer cells or not. In present research, we culture androgen dependent LNCaP cells and androgen independent DU145 cells in vitro, and observe the effects of DHT and TNF-α on the proliferation of the two cells with MTT method. Then, whether trace DHT influences TNF- a inhibiting proliferation of prostate cancer cells or not, and whether AR and IL-6 can involve in the action aforementioned or not are investigated with immunohistochemistry and ELISA, in order to provide some experiment data for using TNF- a curing prostate cancer in clinical.In order to study the effect of trace androgen on proliferation of prostate cancer cells, effects of 100, 10, 1 and 0.1 nmol/L DHT on proliferation of LNCaP and DU145 cells were investigated first of all. Compared with group control (0 mol/L DHT), 100 ~ 0.1 nmol/L DHT stimulates the proliferation of LNCaP cells obviously (increasing by 42.4% ~ 103.6%). As DHT concentration increases, the effect of stimulating proliferation decreases gradually. But 100 ~ 0.1 nmol/L DHT does not influence the proliferation of DU145 cells. Androgen activates signal transductionpathway to play its biological role through combining with androgen receptor. The results of immunohistochemistry show that LNCaP cells express AR, and DU145 cells do not express AR. So, the main reason for the difference in effect of DHT on proliferation of the two kind cells is whether the cells express AR or not.The effect of TNF-aon proliferation of LNCaP and DU145 cells was detected in the next experiment. Compared with group control (0 U/ml TNF- a ), all group of 4000, 1000, 250, 62.5 and 15.6U/ml TNF-a can inhibit the proliferation of LNCaP cells markedly, and as the TNF-a concentration increases, the inhibition heightens gradually. Though the same range of TNF- a concentration also has a repressive effect on proliferation of DU145 cells and shows a dosage dependent effect, the inhibitive effect is inferior and has not significant clinical potency. There exists a different inhibitive effect of the same concentration of TNF- a on the proliferation of LNCaP and DU145 cells (?<0.01). The result confirms that the sensitivity of prostatic cancer cells to TNF- a is concordant with its androgen dependence. It hints whether TNF- a could be used to treat prostate cancer in clinical is in accordance with the androgen sensitivity of prostate cancer cells.After that, we observe whether trace DHT (Inmol/L) has an effect on TNF-a inhibiting proliferation of prostate cancer cells or not. The result shows that DHT eliminates the effect of TNF- a inhibiting proliferation of LNCaP cells, but does not influence proliferation of DU145 cells. This result suggests that when using TNF- a. to treat androgen sensitive prostate cancer, we should administer antiandrogen drug to block the action of androgen (including adrenal origin) completely in order to annul the effect of trace DHT.Many reports show that IL-6 has relation to prostate cancer. Immunohistochemistry experiment shows that both LNCaP and DU145 cells express IL-6. This result infers IL-6 maybe mediate the effects of TNF- a and/or DHT on proliferation of prostate cancer cells. The results of immunohistoch...