Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, Krakow, Poland.
Department of Psychiatry, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
Curr Pharm Biotechnol. 2021;22(5):697-705. doi: 10.2174/1389201021666200710093519.
In cancer, an excessive and uncontrolled process of creating new blood and lymphatic vessels that play a key role in the metastasis process can be observed. The Vascular Endothelial Growth Factor (VEGF-A,-B,-C,-D) family together with their specific receptors (VEGFR-1,-2,- 3) plays a key role in these processes, therefore, it would be reasonable to determine the correct pattern of their expression.
The study aimed to assess the use of salinomycin as an anti-angiogenic and anti-lymphangiogenic drug during endometrial cancer by examining changes in the expression pattern of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2 and VEGFR-3 depending on the treatment period of the Ishikawa endometrial cancer cells with salinomycin in comparison to the control culture.
To determine how influential salinomycin was on the expression of both mRNAs, 1 μM of the drug was added to the cell culture and then it was cultured all together for 12, 24 and 48 hour periods. The cells that made up the control culture were not treated with salinomycin. To determine the changes in the expression profile of the selected genes, we used the microarray, techniques: RTqPCR and ELISA (p<0.05).
For all isoforms of VEGF-A-D as well as receptors of VEGFR-1-3, a decrease in expression under the influence of salinomycin was noted. For VEGF-A and VEGFR-1, the difference in the expression between the culture treated with salinomycin in comparison to the control was statistically significant (p=0.0004). In turn, for VEGF-B, the difference between the culture exposed for 24 hours in comparison to the control (p=0.00000) as well as the comparison between H48 vs. C (p=0.00000) was statistically significant. In reference to VEGF-C, VEGFR-2 and VEGFR-3, the statistical analysis showed the significant difference in expression between the culture incubated with the drug for 12, 24 and 48 hours in comparison to the control as well as between the selected times. For all of these comparisons, p=0.00000 was utilized.
Salinomycin changes the expression pattern of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, and VEGFR-3 in endometrial cancer cells. The obtained results suggest that salinomycin might exert the effect via VEGF signaling pathways.
在癌症中，可以观察到一种过度且不受控制的生成新的血液和淋巴管的过程，这些血管在转移过程中起着关键作用。血管内皮生长因子（VEGF-A、-B、-C、-D）家族及其特定受体（VEGFR-1、-2、-3）在这些过程中起着关键作用，因此，确定它们表达的正确模式是合理的。
本研究旨在通过检测伊希库姆子宫内膜癌细胞在不同处理时间下沙利霉素对 VEGF-A、VEGF-B、VEGF-C、VEGF-D、VEGFR-1、VEGFR-2 和 VEGFR-3 表达模式的影响，评估沙利霉素作为一种抗血管生成和淋巴管生成药物在子宫内膜癌中的作用。
为了确定沙利霉素对两种 mRNA 表达的影响程度，将 1μM 的药物加入细胞培养物中，然后共同培养 12、24 和 48 小时。对照组的细胞未用沙利霉素处理。为了确定所选基因表达谱的变化，我们使用了微阵列、RTqPCR 和 ELISA 技术（p<0.05）。
对于所有 VEGF-A-D 同工型和 VEGFR-1-3 受体，在沙利霉素的影响下，其表达均下降。对于 VEGF-A 和 VEGFR-1，与对照组相比，用沙利霉素处理的培养物中的表达差异具有统计学意义（p=0.0004）。相反，对于 VEGF-B，暴露于 24 小时的培养物与对照组相比（p=0.00000）以及 H48 与 C 相比（p=0.00000）之间的差异具有统计学意义。关于 VEGF-C、VEGFR-2 和 VEGFR-3，统计分析显示，与对照组相比，用药物孵育 12、24 和 48 小时的培养物以及所选时间之间的表达差异具有统计学意义。对于所有这些比较，均使用 p=0.00000。
沙利霉素改变子宫内膜癌细胞中 VEGF-A、VEGF-B、VEGF-C、VEGF-D、VEGFR-1、VEGFR-2 和 VEGFR-3 的表达模式。研究结果表明，沙利霉素可能通过 VEGF 信号通路发挥作用。
