In Vitro Response of Uterine Endometrial Cancer Cell Lines to the Antiestrogen Tamoxifen

Lee, Soon Gone; Nam, Sun Hee; Lee, Kwon Hae

Abstract

Medroxyprogesterone acetate(MPA) is one of the most commonly used hormonal agents for the treatment of advanced or recurrent endometrial adenocarcinoma. However, the progesterone receptor content of endometrial carcinoma varies directly to the degree of differentiation and inversely with stage of the tumor. Thus one would predict that MPA therapy would be less effective in advanced and poorly differentiated tumors. In addition, MPA has been shown to reduce progesterone receptor content of both normal and malignant endometrial cells, which could result in loss of hormone responsiveness. Tamoxifen, which is often used in breast cancer therapy, has also been used in the treatment of patients with advanced and recurrent endometrial carcinoma. Tamoxifen is known to have some estrogenic effects at low concentration and one of these effects is induction of progesterone receptor both in normal and malignant endometrium. This property has focused interest on sequential or simultaneous use of tamoxifen and MPA in the therapy of endometrial carcinoma. The growth inhibitory effects of MPA and tamoxifen were tested on six longestablished endometrial carinoma cell line(HEC-1-A, HEC-1-B, RL 95-2, AN3CA, KLE) and on SCHE-1, a new endometrial carcinoma cell line established in our laboratory. MPA and tamoxifen were used in growth experiments either alone, simultaneously or sequentially. The MCF-7 breast cancer cell line was used as a control. Only 20% reduction in cell number was achieved after 10 days of exposure to the drug, even with the highest MPA concentration tested(10micronm) in endometrial carcinoma cell lines. But in MCF-7 cells, 60% reduction in cell number was achieved with the same concentration of MPA(10um). Ten days of feeding with 5micronm tamoxifen produced a 96% reduction in cell number in MCF-7, a 91% reduction in HEC-1-A, a 88% reduction in HEC-1-B, a 98% reduction in AN3CA and a 71% reduction in KLE cultures. In SCHE-1 cultures a 83% reduction in cell growth was seen and no viable cells remainde in RL 95-2 cultures after 10 days of feeding with a 5uM tamoxifen. In AN3CA cultures, simultaneous exposure to 5um tamoxifen and 5um MPA resulted in partial reversal of the tamoxifen-induced growth inhibition. In RL 95-2, HEC-1-A and HEC-1-B cultures, simultaneous use of these drugs had the same effect as tamoxifen alone, whereas in KLE and SCHE-1 cultures a slight additive growth effect was observed. All six endometrial carcinoma cell lines resumed logarithmic growth when medium containing tamoxifen of logarithmic growth under these conditions was slower than that in the other endometrial carcinoma cultures. Our results show that MPA does not have growth inhibitory effects in these endometrial carcinoma cell cultures, whereas tamoxifen has been shown to have potent endometrial carcinoma cells. These findings are of special importance since patients who are most likely to need adjuvant therapy for advanced or recurrent endometrial carcinoma are those with estrogen receptor and progesterone receptor negative tumors.