5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy

Abstract

Colorectal cancer (CRC) is a major cause of mortality that can be treated effectively with chemotherapy and radiotherapy, although resistance to these therapeutic modalities often occurs. Tumor-treating fields (TTFields) can block tumor growth by selectively impairing tumor cell division. In this study, we investigated the mechanism by which 5-fluorouracil (5-FU) sensitizes tumor cells to TTFields. Human HCT116 and SW480 CRC cells were treated with 5-FU and/or TTFields, and characterized in vitro in terms of cell viability, apoptosis through reactive oxygen species production, autophagy, and metastatic potentials. The biological effects of 5-FU and/or TTFields were studied via positron emission tomography and computed tomography on xenograft tumor growth and were confirmed with organoid models of patients. Our results revealed that combination treatment with 5-FU and TTFields increased the efficiency of TTFields therapy in colon cancer cells by downregulating signaling pathways associated with cell proliferation, survival, cell invasion, and migration while upregulating pathways mediating apoptosis and autophagic cell death. The novel mechanistic insights gleaned in this study suggest that combination therapy with TTFields and 5-FU may be effective in treating CRC, although safety and efficacy testing in patients with CRC will need to be performed before this strategy can be implemented clinically for TTF-sensitization.

Characterization of the mechanism of Scutellaria baicalensis on reversing radio-resistance in colorectal cancer

“…As one of the most important therapeutic strategies for cancer treatment, radiotherapy plays an important role in the treatment of CRC [ 3 , 4 ]. However, due to side effects such as the low sensitivity of radiotherapy and damage to normal tissues, the problem of radio-resistance has become a key factor limiting the effectiveness of CRC treatments [5] . With this in mind, finding ways to reverse radiotherapy resistance and improve radiotherapy sensitivity is of great clinical value in the treatment of CRC.…”

Assessment of the Influence of 5-fluorouracil on the SMAD4 Gene Expression, Apoptosis induction and DNA Damage in the Human CACO-2 Cell Line

“…Currently, the most effective therapeutic strategies for colorectal cancer include chemotherapy and radiation therapy following resection. Chemotherapy based on 5-uorouracil is used as an adjuvant treatment in most colorectal cancer patients who are at high risk of relapse 12,13 . A common and unresolved problem faced when implementing an adjuvant therapy in patients with colorectal cancer is a phenomenon of multi-drug resistance to chemotherapeutic agents used.…”

Allicin enhances the radiosensitivity of colorectal cancer cells via inhibition of NF‐κB signaling pathway

“…Radiotherapy, as one of the most important strategy of cancer treatment, plays a major role in the treatment of CRC (Tam & Wu, 2019). However, the radiotherapy efficacy of CRC is limited due to low radiosensitivity, radioresistance, and damage to normal colon tissue by high irradiation (Lee et al., 2019). Radiosensitizer is a kind of chemical or pharmaceutical agent that could improve the killing effects of tumor cells combination with radiotherapy.…”