Toma J G, Amerongen H M, Hennes S C, O'Brien M G, McBlain W A, Buzzell G R
J Pineal Res. 1987;4(3):321-38. doi: 10.1111/j.1600-079x.1987.tb00870.x.
Conventional antiandrogen therapy for prostatic cancer generally results in the death of androgen-dependent cells, resulting in shrinkage of the tumor, followed by regrowth of the tumor as androgen-insensitive cells take over. Because of reported antigonadotropic and antineoplastic effects of the pineal hormone melatonin (MEL), we hypothesized that this indole might provide an effective therapy for prostate cancer, as it would be effective against both populations of tumor cells. We used three sublines of the Dunning R3327 rat prostatic adenocarcinoma to determine whether MEL could suppress the growth of these tumors and, if so, by what mechanisms this occurs. In one experiments, we compared the growth of a well-differentiated slow-growing Dunning tumor in rats given MEL combined with the potentiating procedure olfactory bulbectomy (BULBX), with that in rats pinealectomized (PINX) or untreated. Tumor growth in BULBX-MEL rats was significantly suppressed over that in the other two groups, as were the weights of the gonads and accessory sex glands. Tumor morphology, DNA concentration, and androgen receptor concentration and distribution were identical in untreated controls and in BULBX-MEL rats, suggesting that the treatment affected all populations of tumor cells equally. With another strain of well-differentiated slow-growing Dunning tumor, we examined the effects of MEL in rats with and without BULBX. Reproductive parameters were not suppressed in BULBX-MEL rats and, while there was a trend toward slower tumor growth in this group, this was not significant. Intact rats given MEL grew larger tumors than did control rats but, again, differences were not significant. In a third experiment, we examined a fast-growing androgen-insensitive anaplastic Dunning tumor. PINX was without effect on this tumor, but BULBX-MEL resulted in a significant suppression of one of the constants in the logistic equation fitted to the growth curves. This indicates that there were some direct antitumor effects of BULBX-MEL on this tumor strain. We conclude that MEL suppresses growth of some Dunning tumor strains.
前列腺癌的传统抗雄激素疗法通常会导致雄激素依赖细胞死亡，使肿瘤缩小，随后随着雄激素不敏感细胞占据主导，肿瘤会再次生长。鉴于松果体激素褪黑素（MEL）具有抗促性腺激素和抗肿瘤作用的报道，我们推测这种吲哚可能为前列腺癌提供一种有效的治疗方法，因为它对两种肿瘤细胞群体均有效。我们使用了邓宁R3327大鼠前列腺腺癌的三个亚系来确定MEL是否能抑制这些肿瘤的生长，如果可以，其作用机制是什么。在一项实验中，我们比较了给予MEL并联合增强手术嗅球切除术（BULBX）的大鼠中分化良好、生长缓慢的邓宁肿瘤的生长情况，与松果体切除（PINX）或未治疗的大鼠的肿瘤生长情况。BULBX-MEL组大鼠的肿瘤生长明显低于其他两组，性腺和附属性腺的重量也是如此。未治疗的对照组和BULBX-MEL组大鼠的肿瘤形态、DNA浓度、雄激素受体浓度和分布相同，这表明该治疗对所有肿瘤细胞群体的影响相同。对于另一株分化良好、生长缓慢的邓宁肿瘤，我们研究了有无BULBX的大鼠中MEL的作用。BULBX-MEL组大鼠的生殖参数未受到抑制，虽然该组肿瘤生长有减缓趋势，但并不显著。给予MEL的完整大鼠比对照大鼠长出更大的肿瘤，但差异同样不显著。在第三个实验中，我们研究了一种生长迅速、雄激素不敏感的间变性邓宁肿瘤。PINX对该肿瘤无效，但BULBX-MEL导致拟合生长曲线的逻辑方程中的一个常数显著降低。这表明BULBX-MEL对该肿瘤株有一些直接的抗肿瘤作用。我们得出结论，MEL可抑制某些邓宁肿瘤株的生长。
