SKOV3 Invasion Research Articles

Effect of down-regulation of HE4 gene expression on biologic behavior of ovarian cancer cells

To investigate the effects of HE4 gene knockdown on the proliferation, adhesion and invasion of the ovarian cancer cells SKOV3. The knockdown of HE4 gene was performed by RNAi technology. The recombinant plasmids (pSUPER-HE4 shDNAs) were constructed and transfected into human ovarian cancer cells SKOV3. HE4 expression was then identified by real-time PCR and Western blot analysis. The invasion and adhesion ability of transduced cells were determined. In addition, cell proliferation and growth were analyzed by colonies formation assay. Knockdown of HE4 was achieved, and further confirmed by real-time PCR and Western blot. The proliferation of HE4-down-regulated cells was not affected, but the invasion ability of the transfected cells was reduced (P < 0.05) and the adhesion ability was also reduced to 27.3%. HE4 expression is down-regulated effectively by the constructed HE4 shDNA, and thus knockdown of HE4 inhibits the adhesion and invasion of SKOV3 cells.

Tyroservatide therapy for tumor invasion and metastasis of human ovarian carcinoma and colon carcinoma

Tyroservatide (YSV) is an active, low-molecular-weight peptide shown to have antimetastasic effects on experimental melanoma and lung carcinoma. This study was carried out to evaluate the therapeutic effects of YSV on tumor invasion and metastasis of ovarian carcinoma and colon carcinoma and explore its antitumor mechanism of action. In vivo, three metastasis models were established, and YSV inhibited abdominal cavity metastasis of human ovarian carcinoma, and liver metastasis after spleen implantation of human colon carcinoma, in mice. In vitro, YSV inhibited the proliferation, promoted the death of SKOV-3, HT-29, and SW620 cells, and inhibited the adhesion and invasion of these three types of cells. Through zymography, western blot, and reverse transcription-PCR methods, YSV was found to reduce the activity, expression, and mRNA level of matrix metalloproteinase (MMP)-2 and MMP-9. The results showed that YSV can inhibit tumor growth and metastasis of human ovarian carcinoma SKOV-3 and human colon carcinoma HT-29 and SW620. The mechanism of action of YSV may involve the inhibition of proliferation, promotion of death, inhibition of the adhesion and invasion of SKOV-3, HT-29, and SW620 cells by downregulating the expression and activity of MMP-2 and MMP-9.

Inhibin Resistance Is Associated with Aggressive Tumorigenicity of Ovarian Cancer Cells

Malignant ovarian epithelial tumors have been shown to have decreased inhibin production relative to activin production compared with normal ovarian surface epithelial (OSE) cells and nonmalignant ovarian tumors. Activin stimulates proliferation of many ovarian cancer cell lines. Inhibin antagonizes the action of activin, and inhibin-deficient mice develop gonadal tumors, suggesting that inhibin may be a tumor suppressor. However, its effects on OSE and ovarian cancer cells are unknown. We hypothesize that activin and inhibin are important regulators of biological activity in ovarian cancers. We found that inhibin A decreased murine OSE proliferation, whereas activin A had no effect. Activin A increased the proliferation of four of eight ovarian cancer cell lines (SKOV3, OCC1, OVCAR3, and A2780-s). Inhibin A decreased the proliferation of SKOV3, A2780-s, and OVCAR3 but had no effect on OCC1, ES-2, HEY, A2780-cp, and OVCA429 cells. When injected into nude mice, the inhibin-resistant cancer cell lines resulted in shorter survival time compared with the inhibin-responsive cells. Further investigations on SKOV3 and OCC1 cells showed that activin A increased invasion through Matrigel. Inhibin A decreased both basal and activin-induced proliferation and invasion of SKOV3 but had no effect on OCC1 cells. Reverse transcription-PCR analyses showed that the SKOV3 and OCC1 cells produced activin, but only SKOV3 produced inhibin. Analysis of the activin/inhibin signaling pathways indicated that Smad anchor for receptor activation was elevated in SKOV3 and OCC1 cells and that an up-regulation of the activin receptor expression may explain the inhibin resistance of OCC1 cells. Our results suggest that activin responsiveness may be gained during transformation of OSE cells and that inhibin resistance may contribute to the aggressive behavior of ovarian cancer cells.