Curcumin inhibits malignant behavior of colorectal cancer cells by regulating M2 polarization of tumor-associated macrophages and metastasis associated in colon cancer 1 (MACC1) expression.

The present study was to investigate the underlying mechanism of the antitumor effect of curcumin in colorectal cancer cells, focusing on the M2 polarization of tumor-associated macrophages (TAMs). The effect of curcumin on the malignant behavior of colorectal cancer cells was investigated by WST assay for cell growth, and Transwell assay for cell migration/invasion. THP-1 cells were differentiated into macrophages and coculture with colorectal cancer cells to study the influence of curcumin on M2 polarization, presenting as the levels of ARG1 mRNA, IL-10, and CD163-positive cells. GEO database was searched for the shared altered gene of curcumin in colorectal cells and human monocytes. Molecular docking was used to visualize the binding between curcumin and MACC1. Curcumin restricted the proliferation, apoptosis, and migration/invasion of HCT 116 and SW620 cells. Curcumin attenuated levels of the M2 macrophage markers, CD163 + cells, IL-10 secretion, and ARG1 mRNA. MACC1 was a target of curcumin in colorectal cancer cells, relating to macrophage. Rescue experiments showed that MACC1 overexpression can reverse the antitumor effect of curcumin in colorectal cancer cells and M2 polarization of TAMs. Curcumin's antiproliferative and anti-migratory effects in colorectal cancer cells may be mediated by MACC1 and inhibition of M2 polarization of TAMs.

Autologous culture method improves retention of tumors' native properties.

No current in vitro tumor model replicates a tumor's in vivo microenvironment. A culturing technique that better preserves a tumor's pathophysiological conditions is needed for some important clinical applications, including personalized drug-sensitivity/resistance assays. In this study, we utilized autologous serum or body fluid to build a 3D scaffold and grow a patient's tumor. We named this technique "3D-ACM" (autologous culture method). Forty-five clinical samples from biopsies, surgically removed tumor tissues and malignant body fluids were cultured with 3D-ACM. Traditional 3D-FBS (fetal bovine serum) cultures were performed side-by-side for comparison. The results were that cells cultured in 3D-ACM rebuilt tissue-like structures, and retained their immuno-phenotypes and cytokine productions. In contrast, the 3D-FBS method promoted mesenchymal cell proliferation. In preliminary chemo drug-sensitivity assays, significantly higher mortality was always associated with FBS-cultured cells. Accordingly, 3D-ACM appears to more reliably preserve a tumor's biological characteristics, which might improve the accuracy of drug-testing for personalized cancer treatment.

Effect of cytokine-induced killer cells on immune function in patients with lung cancer.

Cytokine-induced killer (CIK) cells have been used as adoptive immunotherapy in cancer. The present study evaluated the effect of CIK cells on immune function in patients with lung cancer. Patients were divided into three groups, according to the treatment received prior to CIK cell treatment: CIK group (no prior treatment), Che-Sur group (prior chemotherapy and surgery) and Che-Rad group (prior chemotherapy and radiotherapy). Following treatment, the average percentage of cluster of differentiation (CD)3+CD4+, CD3+, natural killer (NK) and NKT cells in peripheral blood was significantly higher than that prior to CIK treatment in the Che-Sur and CIK groups, and the levels of interferon-γ in serum were significantly higher than those prior to CIK treatment in the Che-Sur and CIK groups. On the contrary, the levels of interleukin-10 had decreased in these groups following CIK treatment. Subsequently, patients were divided into three groups according to the percentage of CD3+CD56+ CIK cells that were administered to the patients. The number of NK and NKT cells increased with increasing number of CD3+CD56+ cells. The patients in the CIK and Che-Sur groups were the most benefited ones following CIK treatment, contrarily to those in the Che-Rad group, since the increase in the number of CD3+CD56+ CIK cells in the aforementioned patients enhanced the number of NK cells, which exhibit antitumor activity.

Synergistic anti-tumor effect of KLF4 and curcumin in human gastric carcinoma cell line.

Kruppel-like factor 4 is a transcription factor which plays an important role in development and progression of various carcinomas. Curcumin characterized by excellent anti-cancer properties is regarded as a serviceable natural compound used in carcinoma therapy. This study aimed at exploring the impact of KLF4 overexpression in cooperation with curcumin on the proliferation, apoptosis and invasion of human gastric carcinoma BGC- 823 cells. Flow cytometry analysis, CCK-8 assays, transwell assays and Western blot results showed that KLF4 overexpression combined with curcumin had significant anti-proliferation, pro-apoptosis and anti-invasion effects on BGC-823 cells. We also found that KLF4 had synergistic effects with curcumin, better promoting apoptosis and inhibiting proliferation and invasion of gastric carcinona cells. These results indicate that KLF4 could be used as a potential therapeutic target; curcumin could act as an auxiliary and provide a promising therapeutic strategy in stomach cancer.