Dual role of macrophages in the response of C26 colon carcinoma cells to 5-fluorouracil administration

Pătraș, Laura; Sesărman, Alina; Licărete, Emilia; Luca, Lavinia; Alupei, Marius Costel; Rákosy-Tican, Elena; Banciu, Manuela

doi:10.3892/ol.2016.4708

Cited by 18 publications

(27 citation statements)

References 46 publications

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“…Firstly, the expression of the inflammatory transcription factor, NF-κB was assessed as the active form as well as total protein (as the active and inactive form). It is known that NF-κB is a pleiotropic transcriptional regulator constitutively expressed and activated in most colon carcinoma cells including C26 cells (39). This protein controls the expression of numerous genes encoding for growth factors (VEGF and FGF), cytokines and chemokines (TNF-α and IL-8), and metalloproteinases, which are involved in tumor inflammation, angiogenesis, cell proliferation, tumor survival and chemoresistance (40,41).…”

Section: Discussionmentioning

confidence: 99%

Tumor-associated macrophages favor C26 murine colon carcinoma cell proliferation in an oxidative stress-dependent manner

et al. 2017

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The role of tumor-associated macrophages (TAMs) in the development of colon carcinoma is still controversial. Therefore, the present study aimed to investigate the TAM‑driven processes that may affect colon cancer cell proliferation. To achieve this purpose, murine macrophages were co-cultured with C26 murine colon carcinoma cells at a cell density ratio that approximates physiological conditions for colon carcinoma development in vivo. In this respect, the effects of TAM-mediated angiogenesis, inflammation and oxidative stress on the proliferative capacity of C26 murine colon carcinoma cells were studied. To gain insight into the TAM-driven oxidative stress, NADPH oxidase, the main pro-oxidant enzyme in macrophages, was inhibited. Our data revealed that the stimulatory effects of TAMs on C26 cell proliferation may be related mainly to their pro-oxidant actions exerted by NADPH oxidase activity, which maintains the redox status and the angiogenic capacity of the tumor microenvironment. Additionally, the anti-inflammatory and pro-angiogenic effects of TAMs on tumor cells were found to create a favorable microenvironment for C26 colon carcinoma development and progression. In conclusion, our data confirmed the protumor role of TAMs in the development of colon carcinoma in an oxidative stress-dependent manner that potentiates the angiogenic capacity of the tumor microenvironment. These data may offer valuable information for future tumor-targeted therapies based on TAM 're-education' strategies.

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Section: Discussionmentioning

confidence: 99%

Tumor-associated macrophages favor C26 murine colon carcinoma cell proliferation in an oxidative stress-dependent manner

et al. 2017

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“…After 12 hours of incubation, the cells were treated with DOX, DOX-LCL and the two DOX-CUR-LCL formulations, for an additional 48 hours. The in vitro cytotoxicity of different treatments applied on C26 cells was evaluated by using the ELISA BrdU-colorimetric immunoassay according to the manufacturer’s instructions, as previously described 37. Results are expressed as percentage of inhibition of cell proliferation compared to that of untreated C26 cells and are presented as the mean ± standard deviation of triplicate measurements.…”

Section: Methodsmentioning

confidence: 99%

Development of antiproliferative long-circulating liposomes co-encapsulating doxorubicin and curcumin, through the use of a quality-by-design approach

Tefas

Sylvester

Tomuță

et al. 2017

DDDT

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The aim of this work was to use the quality-by-design (QbD) approach in the development of long-circulating liposomes co-loaded with curcumin (CUR) and doxorubicin (DOX) and to evaluate the cytotoxic potential of these liposomes in vitro using C26 murine colon carcinoma cell line. Based on a risk assessment, six parameters, namely the phospholipid, CUR and DOX concentrations, the phospholipid:cholesterol molar ratio, the temperature during the evaporation and hydration steps and the pH of the phosphate buffer, were identified as potential risk factors for the quality of the final product. The influence of these variables on the critical quality attributes of the co-loaded liposomal CUR and DOX was investigated: particle size, zeta potential, drug loading and entrapment efficiency. For this, a 26−2 factorial design was employed to establish a proper regression model and to generate the contour plots for the responses. The obtained data served to establish the design space for which different combinations of variables yielded liposomes with characteristics within predefined specifications. The validation of the model was carried out by preparing two liposomal formulations corresponding to the robust set point from within the design space and one outside the design space and calculating the percentage bias between the predicted and actual experimental results. The in vitro antiproliferative test showed that at higher CUR concentrations, the liposomes co-encapsulating CUR and DOX had a greater cytotoxic effect than DOX-loaded liposomes. Overall, this study showed that QbD is a useful instrument for controlling and optimizing the manufacturing process of liposomes co-loaded with CUR and DOX and that this nanoparticulate system possesses a great potential for use in colon cancer therapy.

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“…1A-E and Table 1). To further study the earlier suggested antitumor activities of LCL-PLP 11,12,18 as well as of 5-FU 21 via modulation of key protumor processes, the effects of the LCL-PLP C LCL-5-FU in C26 colon carcinoma-bearing mice were investigated with regard to intratumor production of inflammatory, angiogenic and oxidative stress markers. Our data provided confirmatory evidence for the anti-inflammatory and anti-angiogenic mode of action of the antitumor activity of the combined liposomal drug therapy in colon carcinoma in vivo.…”

Section: Discussionmentioning

confidence: 99%

Liposomal prednisolone phosphate potentiates the antitumor activity of liposomal 5-fluorouracil in C26 murine colon carcinomain vivo

Pătraș

Sylvester

Lupuţ

et al. 2017

Cancer Biology & Therapy

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The antitumor efficacy of 5-fluorouracil (5-FU) in advanced colorectal cancer (CRC) is hindered not only by the low therapeutic index, but also by tumor cell resistance to this cytotoxic drug. Therefore, to enhance the 5-FU antitumor activity, the present research used a novel tumor-targeted therapy based on the co-administration of 5-FU encapsulated in long-circulating liposomes (LCL-5-FU) together with liposomal prednisolone phosphate (LCL-PLP), a formulation with known anti-angiogenic actions on C26 murine colon carcinoma cells. Thus, we assessed the in vivo effects of the combined liposomal drug therapy on C26 carcinoma growth as well as on the production of molecular markers with key roles in tumor development such as angiogenic, inflammatory, and oxidative stress molecules. To get further insight into the polarization state of tumor microenvironment after the treatment, we determined the IL-10/IL-12p70 ratio in tumors. Our results showed that combined liposomal drug therapy inhibited almost totally tumor growth and was superior as antitumor activity to both single liposomal drug therapies tested. The antitumor efficacy of the combined therapy was mainly related to the anti-angiogenic and anti-inflammatory actions on C26 carcinoma milieu, being favored by its controlling effect on intratumor oxidative stress and the skewing of polarization of tumor microenvironmental cells toward their antineoplastic phenotypes. Thus, our study unveils a promising treatment strategy for CRC that should be furthermore considered.

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Dual role of macrophages in the response of C26 colon carcinoma cells to 5-fluorouracil administration

Cited by 18 publications

References 46 publications

Tumor-associated macrophages favor C26 murine colon carcinoma cell proliferation in an oxidative stress-dependent manner

Tumor-associated macrophages favor C26 murine colon carcinoma cell proliferation in an oxidative stress-dependent manner

Development of antiproliferative long-circulating liposomes co-encapsulating doxorubicin and curcumin, through the use of a quality-by-design approach

Liposomal prednisolone phosphate potentiates the antitumor activity of liposomal 5-fluorouracil in C26 murine colon carcinomain vivo

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