In vitro growth regulation of endometrial carcinoma cells by tamoxifen and medroxyprogesterone acetate.
In vitro growth regulation of endometrial carcinoma cells by tamoxifen and medroxyprogesterone acetate.
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DOI：
10.1016/0090-8258(88)90030-3
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发表时间：
1988-06
影响因子：
4.7
通讯作者：
Seija E. Grenman;James A. Roberts;Barry G. England;Matti Grönroos;Thomas E. Carey
中科院分区：
文献类型：
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作者：
Seija E. Grenman;James A. Roberts;Barry G. England;Matti Grönroos;Thomas E. Carey
研究了醋酸甲羟孕酮（MPA）和他莫昔芬（TAM）对三种已建立的子宫内膜癌细胞系（HEC-1、KLE和RL95-2）和我们实验室新建立的子宫内膜癌细胞系UM-EC-1的生长抑制作用。MPA和TAM可单独、同时或依次用于生长实验。MCF-7乳腺癌细胞系作为对照。子宫内膜癌细胞系对0.1 ~ 10 μM MPA无明显敏感性。相比之下，5 μM TAM对HEC-1和KLE培养物的生长抑制率分别为83%和70%，而UM-EC-1的生长抑制率为99.7%，RL95-2的生长抑制率为100%。TAM诱导的生长抑制是可逆的，因为当TAM从培养基中去除时，所有细胞系恢复对数生长。在培养基中添加17-β-雌二醇（E2）不会加速恢复，同时添加TAM和E2时，TAM诱导的生长抑制未见逆转。这与我们的发现是一致的，除了MCF-7，这些细胞系在这些实验时进行的检测中没有显示出可检测的雌激素受体（ER）活性。当TAM和MPA连续处理时，将含TAM的培养基替换为含MPA的培养基时，所有细胞系都恢复了对数生长。同时暴露于5μMMPA和5μMTAM只在KLE培养中产生轻微的加性生长抑制作用。我们的研究结果表明，MPA在这些子宫内膜癌细胞培养中没有生长抑制作用，而TAM具有强大的生长抑制作用，不被雌激素逆转，因此可能通过不同于阻断ER的机制介导。UM-EC-1细胞系的体外结果与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。
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 μM MPA. In contrast, 10 days exposure to 5 μM 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-β-estradiol (E2) to the culture medium did not accelerate recovery, and reversal of TAM-induced growth inhibition was not seen when TAM and E2were 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 5μMMPA and 5μMTAM 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 growth inhibitory effect that is not reversed by estrogen and may thus be mediated through a mechanism different from blockade of ER.In vitroresults 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.