Grenman S E, Roberts J A, England B G, Grönroos M, Carey T E
Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor 48109.
Gynecol Oncol. 1988 Jun;30(2):239-50. doi: 10.1016/0090-8258(88)90030-3.
The growth inhibitory effects of medroxyprogesterone acetate (MPA) and tamoxifen (TAM) were tested on three long-established endometrial carcinoma cell lines (HEC-1, KLE, and RL95-2) and on UM-EC-1, a new endometrial carcinoma cell line established in our laboratory. MPA and TAM were used in growth experiments either alone, simultaneously, or sequentially. The MCF-7 breast cancer cell line was used as a control. None of the endometrial carcinoma cell lines showed significant sensitivity to 0.1-10 microM MPA. In contrast, 10 days exposure to 5 microM TAM induced 83 and 70% growth inhibition in HEC-1 and KLE cultures, whereas the growth of UM-EC-1 was inhibited by 99.7% and RL95-2 cultures by 100%. TAM-induced growth inhibition was reversible since all cell lines resumed logarithmic growth when TAM was removed from the culture medium. Addition of 17 beta-estradiol (E2) to the culture medium did not accelerate recovery, and reversal of TAM-induced growth inhibition was not seen when TAM and E2 were added simultaneously. This is consistent with our finding that, except for MCF-7, these cell lines did not show detectable estrogen receptor (ER) activity in assays performed at the time of these experiments. When treated sequentially with TAM and MPA, all cell lines resumed logarithmic growth when medium containing TAM was replaced with medium containing MPA. Simultaneous exposure to 5 microM MPA and 5 microM TAM resulted in a slight additive growth inhibitory effects only in KLE cultures. Our results show that MPA does not have growth inhibitory effects in these endometrial carcinoma cell cultures, whereas TAM exerts a potent inhibitory effect that is not reversed by estrogen and may thus be mediated through a mechanism different from blockade of ER. In vitro results with the UM-EC-1 cell line correlated with the clinical response of the cell line donor. Her disease progressed during postoperative MPA therapy, but subsequently she responded to TAM therapy.
在三种长期建立的子宫内膜癌细胞系（HEC - 1、KLE和RL95 - 2）以及我们实验室新建立的子宫内膜癌细胞系UM - EC - 1上测试了醋酸甲羟孕酮（MPA）和他莫昔芬（TAM）的生长抑制作用。MPA和TAM单独、同时或序贯用于生长实验。MCF - 7乳腺癌细胞系用作对照。没有一种子宫内膜癌细胞系对0.1 - 10微摩尔/升的MPA表现出显著敏感性。相比之下，10天暴露于5微摩尔/升的TAM可使HEC - 1和KLE培养物中的生长分别受到83%和70%的抑制，而UM - EC - 1的生长受到99.7%的抑制，RL95 - 2培养物则受到100%的抑制。TAM诱导的生长抑制是可逆的，因为当从培养基中去除TAM时，所有细胞系都恢复了对数生长。向培养基中添加17β - 雌二醇（E2）并不能加速恢复，并且当同时添加TAM和E2时，未观察到TAM诱导的生长抑制的逆转。这与我们的发现一致，即在这些实验进行时所做的检测中，除了MCF - 7外，这些细胞系未显示出可检测到的雌激素受体（ER）活性。当用TAM和MPA序贯处理时，当含TAM的培养基被含MPA的培养基替换时，所有细胞系都恢复了对数生长。同时暴露于5微摩尔/升的MPA和5微摩尔/升的TAM仅在KLE培养物中产生了轻微的相加生长抑制作用。我们的结果表明，MPA在这些子宫内膜癌细胞培养物中没有生长抑制作用，而TAM发挥了强大的抑制作用，且不受雌激素逆转，因此可能是通过不同于ER阻断的机制介导的。UM - EC - 1细胞系的体外结果与该细胞系供体的临床反应相关。她的疾病在术后MPA治疗期间进展，但随后她对TAM治疗有反应。
