MC38 Cancer Cells Research Articles

Alpha-galactosylceramide loaded tumor cells in combination with TLR9 agonists induce potent anti-tumor responses in a murine model of colon cancer

Objective To design a new cancer vaccine by using alpha-galactosylceramide （α-Galcer,α-GC） loaded tumor cells in combination with TLR 9 ligand and to evaluate its therapeutic effects on colon canc-er in mice.Methods MC38 cells were transfected with lentivirus （GFP-CD1d） to prepare CD1d-MC38 cells. The expression of CD1d molecules in CD1d-MC38 cells was detected by fluorescence microscopy , RT-PCR and flow cytometry.The sorted CD1d-MC38 cells were loaded with α-Galcer to prepare CD1d-MC38/α-GC complex. Flow cytometry was performed to evaluate the efficiency of combination .A mouse model of colon cancer was es-tablished to investigate the therapeutic effects of α-Galcer loaded tumor cells in combination with TLR 9 ligand （ CD1d-MC38/α-GC＋CpG1826） on colon cancer in mice by analyzing tumor growth and mice survival time .Im-munohistochemical staining was used to detect CD 4＋T and CD8＋T infiltrating lymphocytes in tumor tissues .Re-sults The MC38 cancer cells that expressed CD 1d and GFP were successfully constructed , among which 98.10%±2.53%were positive for CD1d.Moreover, the CD1d-MC38 cells could combine with α-Galcer effec-tively in a dose and time dependent manner .Compared with PBS treated group ,α-GC treated group and TLR9 ligand treated group , the experimental vaccine strategy was sufficient to inhibit the growth of established tumors and prolong survival of tumor-bearing mice （P〈0.01）.Immunohistochemistry analysis revealed that levels of CD4＋T cells and CD8＋T cells in experiment group were significantly higher than those in groups treated with PBS,α-GC and TLR9 ligand （P〈0.01）.Conclusion CD1d-MC38/α-GC in combination with CpG1826 could efficiently inhibit the growth of established tumors and prolong survival of tumor-bearing mice .Immunohisto-chemistry analysis revealed that CD 4＋T cells and CD8＋T cells played important roles in anti-tumor immunity. Key words: iNKT cells; Dendritic cells; α-Galcer; Cancer vaccine

Curcumin and docosahexaenoic acid block insulin-induced colon carcinoma cell proliferation

Diets high in fish and curcumin are associated with a decreased risk of CRC. Insulin resistance and obesity are associated with increased CRC risk and higher reoccurrence rates. We utilized cell culture to determine if dietary compounds could reduce insulin-induced cell proliferation comparing the response in normal and metastatic colon epithelial cells. We treated model normal murine colon epithelial cells (YAMC) and adenocarcinoma cells (MC38) with docosahexaenoic acid (DHA) or curcumin alone and then co-treatments of the diet-derived compound and insulin were combined. Cell proliferation was stimulated with insulin (1ug/mL) to model insulin resistance in obesity. Despite the presence of insulin, proliferation was reduced in the MC38 cells treated with 10μM curcumin (p<0.001) and 50μM DHA (p<0.001). Insulin stimulated MAPK and MEK phosphorylation was inhibited by DHA and curcumin in MC38 cancer cells. Here we show that curcumin and DHA can block insulin-induced colon cancer cell proliferation in vitro via a MEK mediated mechanism.

Oncolytic poxvirus armed with Fas ligand leads to induction of cellular Fas receptor and selective viral replication in FasR-negative cancer

The TNF superfamily members including Fas ligand and TRAIL have been studied extensively for cancer therapy, including as components of gene therapy. We examined the use of FasL expression to achieve tumor selective replication of an oncolytic poxvirus (vFasL) and explored its biology and therapeutic efficacy for FasR− and FasR+ cancers. Infection of FasR+ normal and MC38 cancer cells by vFasL led to abortive viral replication due to acute apoptosis and subsequently displayed both reduced pathogenicity in non-tumor bearing mice and reduced efficacy in FasR+ tumor-bearing mice. Infection of FasR− B16 cancer cells by vFasL led to efficient viral replication, followed by late induction of FasR and subsequent apoptosis. Treatment with vFasL compared to its parental virus (vJS6) led to increased tumor regression and prolonged survival of mice with FasR− cancer (B16), but not with FasR+ cancer (MC38). The delayed induction of FasR by viral infection in FasR− cells provides for potential increased efficacy beyond the limit of the direct oncolytic effect. FasR induction provides one mechanism for tumor selective replication of oncolytic poxviruses in FasR− cancers with enhanced safety. The overall result is both a safer and more effective oncolytic virus for FasR− cancer.

The inhibitory effect of diarylpropionitrile, a selective agonist of estrogen receptor beta, on the growth of MC38 colon cancer line

The protective role of estrogens in the colon carcinogenesis has been suggested for many years and attributed mainly to estrogen receptor beta (ERβ). However, the direct effect of estrogens and their action through ERβ on the growth of colon cancer have been rarely studied. The aim of this study was to examine the effect of various concentrations (10 −4–10 −12 M) of diarylpropionitrile (DPN) – a selective agonist of ERβ – on the growth of murine MC38 colon cancer line. Moreover, the aim of this paper was the immunohistochemical assessment of estrogen and progesterone receptor expression in human colon tissues and in MC38 cells (only ERβ). We found that DPN induced a growth inhibition of MC38 cancer (50–94% of control group) at the highest (10 −4 M) and two lowest concentrations (10 −11 and 10 −12 M). Furthermore, we detected a nuclear-cytoplasmic expression of ERβ in human normal and neoplastic colon tissues and in the studied MC38 cancer cells. The inhibitory effect of DPN on the growth of MC38 colon cancer line suggests a possibility of using a selective estrogen receptor agonist in the treatment of colon cancer.