División de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, Mexico.
Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico; Facultad de Ciencias de la Salud, Universidad Anáhuac México Norte, Huixquilucan, Estado de México, Mexico.
Arch Med Res. 2020 Jan;51(1):65-75. doi: 10.1016/j.arcmed.2019.12.003. Epub 2020 Feb 22.
Calreticulin is a chaperone and master regulator of intracellular calcium homeostasis. Several additional functions have been discovered. Human and parasite calreticulin have been shown to suppress mammary tumor growth in vivo. Here, we explored the capacity of recombinant Taenia solium calreticulin (rTsCRT) to modulate cancer cell growth in vitro.
We used different concentrations of rTsCRT to treat cancer cell lines and analyzed viability and colony formation capacity. We also tested the combination of the IC or IC doses of rTsCRT and of the chemotherapeutic drug 5-fluorouracil on MCF7 and SKOV3 cell lines. As a control, the non-tumorigenic cell line MCF10-A was employed. The effect of the drug combinations was also assessed in cancer stem-like cells. Additionally, scavenger receptor ligands were employed to identify the role of this receptor in the rTsCRT anti-tumoral effect.
rTsCRT has a dose-dependent in vitro anti-tumoral effect, being SKOV3 the most sensitive cell line followed by MCF7. When rTsCRT/5-fluorouracil were used, MCF7 and SKOV3 showed a 60% reduction in cell viability; colony formation capacity was also diminished. Treatment of cancer stem-like cells from MCF7 showed a higher reduction in cell viability, while those from SKOV3 were more sensitive to colony disaggregation. Finally, pharmacological inhibition of the scavenger receptor, abrogated the reduction in viability induced by rTsCRT in both the parental and stem-like cells.
Our data suggest that rTsCRT alone or in combination with 5-fluorouracil inhibits the growth of breast and ovarian cancer cell lines through its interaction with scavenger receptors.
钙网织蛋白是细胞内钙稳态的伴侣和主要调节剂。已经发现了其他一些额外的功能。已经证明人和寄生虫钙网织蛋白能够在体内抑制乳腺肿瘤的生长。在这里，我们探索重组猪带绦虫钙网织蛋白（rTsCRT）在体外调节癌细胞生长的能力。
我们使用不同浓度的 rTsCRT 处理癌细胞系，并分析其活力和集落形成能力。我们还测试了 rTsCRT 的 IC 或 IC 剂量与化疗药物 5-氟尿嘧啶对 MCF7 和 SKOV3 细胞系的组合。作为对照，使用非致瘤细胞系 MCF10-A。还评估了药物组合对癌症干细胞样细胞的影响。此外，还使用了清道夫受体配体来确定该受体在 rTsCRT 抗肿瘤作用中的作用。
rTsCRT 在体外具有剂量依赖性的抗肿瘤作用，其中 SKOV3 是最敏感的细胞系，其次是 MCF7。当 rTsCRT/5-氟尿嘧啶联合使用时，MCF7 和 SKOV3 的细胞活力降低了 60%；集落形成能力也降低了。来自 MCF7 的癌症干细胞样细胞的处理显示出更高的细胞活力降低，而来自 SKOV3 的细胞对集落分散更为敏感。最后，清道夫受体的药理学抑制消除了 rTsCRT 在亲本和干细胞样细胞中诱导的活力降低。
我们的数据表明，rTsCRT 单独或与 5-氟尿嘧啶联合使用，通过与清道夫受体相互作用，抑制乳腺癌和卵巢癌细胞系的生长。
