Paclitaxel Potentiates the Anticancer Effect of Cetuximab by Enhancing Antibody-Dependent Cellular Cytotoxicity on Oral Squamous Cell Carcinoma Cells In Vitro

Abstract

Administration of cetuximab (C-mab) in combination with paclitaxel (PTX) has been used for patients with head and neck squamous cell carcinoma (SCC) clinically. In this study, we attempted to clarify the molecular mechanisms of the enhancing anticancer effect of C-mab combined with PTX on oral SCC cells in vitro. We used two oral SCC cells (HSC4, OSC19) and A431 cells. PTX alone inhibited cell growth in all cells in a concentration-dependent manner. C-mab alone inhibited the growth of A431 and OSC19 cells at low concentrations, but inhibited the growth of HSC4 cells very weakly, even at high concentrations. A combined effect of the two drugs was moderate on A431 cells, but slight on HSC4 and OSC19 cells. A low concentration of PTX enhanced the antibody-dependent cellular cytotoxicity (ADCC) induced by C-mab in all of the cells tested. PTX slightly enhanced the anticancer effect of C-mab in this ADCC model on A431 and HSC4 cells, and markedly enhanced the anticancer effect of C-mab on OSC19 cells. These results indicated that PTX potentiated the anticancer effect of C-mab through enhancing the ADCC in oral SCC cells.

Effectiveness of cetuximab as preemptive postsurgical therapy for oral squamous cell carcinoma patients with major risk: a single‐center retrospective cohort study

“…Panitumumab, a complete human IgG2 antibody, is effective for colorectal cancer, but not for head and neck cancers, including oral cancer [ 24 ]. We have recently suggested that the main action of cetuximab in oral cancer may be immunological reaction, such as ADCC, rather than signaling blockade [ 11 ].…”

“…cetuximab is an antibody to epidermal growth factor receptor (EGFR) that is used for treatment of metastatic colorectal cancer, metastatic non-small cell lung cancer, and head and neck cancer. We have suggested that the main effect of cetuximab in patients with OSCC may be immunological, such as antibody-dependent cellular cytotoxicity (ADCC), rather than signaling blockade [ 11 ]. In OSCC patients with local recurrence, lymph node metastasis, or distal metastasis, we hypothesized that dormant cancer cells that could not be detected before or during initial treatment might grow after the primary treatment and develop into a visible tumor.…”

The role of non‐coding RNAs in drug resistance of oral squamous cell carcinoma and therapeutic potential

“…Therefore, PTX is often used as an adjunct drug to other anticancer drugs in the treatment of OSCC. For example, PTX enhanced the toxicity of cetuximab to OSCC cells and induced apoptosis of OSCC cells [ 47 ]. However, the use of chemotherapeutic agents in OSCC is limited by the development of intrinsic or acquired drug resistance in patients.…”

Current Perspectives on Taxanes: Focus on Their Bioactivity, Delivery and Combination Therapy

“…It competitively inhibits binding of the epidermal growth factor and tumor growth factor-alpha, by which it reduces tumor growth, and cancer cell migration and spreading. Antibody-dependent cellular cytotoxicity, the main mechanism of anticancer action of cetuximab, can be further increased by paclitaxel [ 148 ]. Co-administration of cetuximab and paclitaxel was reported to be effective not only for the treatment of head and neck carcinoma but also for cervical, esophageal, urothelial, or non-small cell lung carcinoma, on which there are currently active clinical trials [ 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 ].…”