I want to inhibit colon cancer growth with siRNA's which target metastatic proteins but some articles have shown that combining with some inhibitors will raise the efficiency of the therapy. Because of this reason, I want to learn the best inhibitors against colon cancer cells.
We successfully used DZNep to induce apoptosis in human colon cancer cells.
Pharmacological inhibition of polycomb repressive complex-2 activity induces apoptosis in human colon cancer stem cells. Benoit YD, Witherspoon MS, Laursen KB, Guezguez A, Beauséjour M, Beaulieu JF, Lipkin SM, Gudas LJ. Exp Cell Res. 2013 Jun 10;319(10):1463-70. PMID: 23588203
The following experience might be informative for you!!!
I have the experience of the similar experiment as a graduate a student. Depletion of beta-catenin or c-Myc by small-interfering RNA of HT-29, HCT-116 and SW1222 cells failed to induce the significant blockage of proliferation or apoptotic cell death. This was quite surprising after I confirmed by Western blotting that either molecule was efficiently depleted. I still do not why, given that colon cancer cells tend to show the constitutive activation of canonical beta-catenin/Wnt signal activation and they show the oncogene-addictions.
I would like to add the important information!!!
Given that SSZ (sulfasalazine), the conventional drug for the treatment of patients with ulcerative colitis or rheumatoid arthritis, exhibits tumor shrinking effect in murine gastric adenocarcinoma model via the blockage of xCT cysteine transporter, I strongly recommend the administration of this drugs to nude mice with xenograft model or treatment with this drug in vitro culture.
You may be confused that gastric and colon cancer cells are different each other. However, both tumors largely depend on Wnt/beta-catenin signal pathway in proliferation and survival and furthermore, both tumor cell lines, as far as I know, highly express CD44 variant 8-10 and depend on xCT-CD44 variant-glutathione axis to survive under the high amount of reactive oxygen species.
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