REGRESSION MECHANISMS OF MOUSE FIBROSARCOMA CELLS AFTER INVITRO EXPOSURE TO QUERCETIN - DIMINUTION OF TUMORIGENICITY WITH A CORRESPONDING DECREASE IN THE PRODUCTION OF PROSTAGLANDIN-E2
REGRESSION MECHANISMS OF MOUSE FIBROSARCOMA CELLS AFTER INVITRO EXPOSURE TO QUERCETIN - DIMINUTION OF TUMORIGENICITY WITH A CORRESPONDING DECREASE IN THE PRODUCTION OF PROSTAGLANDIN-E2
复制标题
DOI：
10.1007/bf01741407
复制
发表时间：
1990-09-01
影响因子：
5.8
通讯作者：
KOBAYASHI, H
中科院分区：
文献类型：
--
作者：
OKADA, F;HOSOKAWA, M;KOBAYASHI, H
我们之前曾报道过，小鼠纤维肉瘤BMT-11 cl-9体外暴露于槲皮素后获得了消退（QR）和进展（转移性，QP）克隆[17]。在这项研究中，我们研究了QR克隆与致瘤性QP和BMT-11 cl-9肿瘤克隆相比自发消退的可能机制。我们观察到，BMT-11 cl-9细胞在体外培养过程中产生相对较高量的前列腺素E2（PGE2）。BMT-11cl-9细胞的11个亚克隆的平均产量为9236 ± 0.0000。2829pg/ml，而9个QR克隆的为3411 ± 1.5pg/ml。2213 pg/ml（P <0.02）。吲哚美辛不仅抑制QP克隆（高PGE 2生产者）的体外PGE 2合成，而且还抑制皮下注射（s.c.）QP克隆在小鼠中的生长。肿瘤相关抗原的宿主免疫反应的时间变化进行了测量的细胞毒性T淋巴细胞（CTL）活性检查后，混合淋巴细胞/肿瘤细胞培养的脾细胞从荷瘤小鼠。接种肿瘤后21天，携带QP克隆的小鼠脾脏中的CTL活性突然消失，而接种QR克隆的小鼠的脾细胞保留了它们的CTL活性。我们确定，这些回归因子克隆的回归机制不是由于预先存在的膜抗原的任何定性或定量增加，也不是由于QR克隆的细胞表面上出现新抗原;也不是由于QR克隆对自然杀伤细胞、淋巴因子激活的杀伤细胞和巨噬细胞的易感性增强。这些结果表明，QR克隆的回归机制可能是减少抑制宿主对肿瘤相关抗原的反应所造成的减少生产的PGE 2的QR克隆。
We have previously reported that both regressor (QR) and progressor (metastatic, QP) clones were obtained after the in vitro exposure of a mouse fibrosarcoma BMT-11 cl-9 to quercetin [17]. In this study, we investigated possible mechanisms of spontaneous regression of QR clones as compared with tumorigenic QP and BMT-11 cl-9 tumor clones. We observed that BMT-11 cl-9 cells produced relatively high amounts of prostaglandin E2 (PGE2) during in vitro culture. The average production by 11 subclones of BMT-11 cl-9 cells was 9236 .+-. 2829 pg/ml whereas that by 9 QR clones was 3411 .+-. 2213 pg/ml (P < 0.02). Indomethacin not only inhibited in vitro PGE2 synthesis by QP clones (high-PGE2 producers) but also the s.c. growth of QP clones in mice. Chronological changes in host immune responses to tumor-associated antigen were measured by cytotoxic T lymphocyte (CTL) activity examined after mixed lymphocyte/tumor cell culture of spleen cells obtained from tumor-bearing mice. The CTL activity disappeared abruptly in the spleen of QP-clone-bearing mice 21 days after the inoculation of tumors, whereas the spleen cells of QR-clone-inoculated mice retained their CTL activity. We determined that the mechanism responsible for the regression of these regressor clones is not due to any qualitative or quantitative increase in pre-existing membrane antigens, nor the emergence of new antigen(s) on the cell surface of the QR clones; nor was it due to enhanced susceptibility of QR clones to natural killer cells, lymphokine-activated killer cells and macrophages. These findings suggest that the regression mechanism of QR clones may be the diminished inhibition of host response to tumor-associated antigen caused by reduced production of PGE2 by QR clones.