The squamous cell carcinoma cell line NOKT-1 was successfully established from the right tongue of a 74-yearold Japanese man. Pathological diagnosis of the original tumor was moderately differentiated squamous cell carcinoma. NOKT-1 cells were transplanted subcutaneously into nude mice and xenograft was formed. In addition, the NOKT-1-XG cell line was established from the transplanted tumor of NOKT-1 cells. NOKT-1 cells and NOKT-1-XG cells were epithelial neoplastic and pleomorphic cells, which were similar. Immunocytochemistry revealed that NOKT-1 and NOKT-1-XG cells were CK17 and human mitochondria positive. To authenticate the NOKT-1 cell line and NOKT-1-XG cell line, we examined cross-contamination with other cell lines using short tandem repeat analysis, the results of which showed that NOKT-1 and NOKT-1-XG are new cell lines. Four of the 16 loci, corresponding to 25%, were different between these two cell lines, which indicates that the NOKT-1 genome was altered by transplantation. Moreover, in AM, NOKT-1 did not have a Y chromosome, whereas NOKT-1-XG had. Despite the genetic differences, a collagen gel droplet-embedded culture drug susceptibility test demonstrated that NOKT-1 cells derived from the original tumor and the NOKT-1-XG cell line had the same sensitivity. This cell line could be very useful for the development of immunotherapy and chemotherapy regimens and research on cancer etiology.
Background/Aim: The mechanisms through which cetuximab (cMab) coadministration with paclitaxel (PTX) enhances antitumor efficacy remain unclear. We examined the mechanism of the antitumor enhancing effect of cMab by determining changes in gene expression in the PI3K-AKT pathway. Materials and Methods: Eight human oral squamous cell carcinoma (OSCC) cell lines were cultured three-dimensionally and exposed to PTX + cMab. The expression levels of PTEN mRNA in OSCC cell lines after anticancer drug treatment were assessed using real-time PCR. PTEN mRNA expression levels were also confirmed after administration of PTX + cMab in vivo. Western blot analysis was used to confirm the results at the protein level. Results: PTEN mRNA and protein expression were significantly increased only in the cell lines with high sensitivity to PTX + cMab, and similar results were observed in vivo. Conclusion: PTEN activation may enhance the antitumor effect of PTX + cMab.Recent studies have reported the remarkable benefits of coadministration of paclitaxel (PTX), a taxane anticancer drug, and cetuximab (cMab), an anti-human epidermal growth factor receptor (EGFR) antibody, for the treatment of recurrent/metastatic oral cancer (1). In particular, the response rate to PTX+cMab therapy has been reported to be 60% in patients whose disease had progressed after second-line treatment for platinum-refractory head and neck squamous cell carcinoma with nivolumab, an immune checkpoint inhibitor for human programmed cell death-1 (PD-1) (2). However, there are currently no clear biomarkers for predicting the effect of cMab and PTX coadministration and the mechanisms associated with the enhancement of antitumor effects.The EGFR signaling pathway, which is the pathway targeted by cMab includes the RAS signaling pathway involved in the proliferation of cancer cells and the Phosphoinositide 3-kinase (PI3K)-AKT pathway involved in the anti-apoptosis, invasion, and migration of cancer cells (3,4). The activation of the PI3K-AKT pathway starts with the phosphorylation of PI3K; subsequently, the phosphorylation of AKT promotes anti-apoptosis, invasion, and migration of cancer cells (4). Conversely, phosphatase and tensin homolog (PTEN) has been shown to inhibit cancer cell proliferation by inhibiting the PI3K-AKT pathway (5). Although many studies have shown that low PTEN expression is involved in cMab resistance (6-9), there are also reports that PTX resistance, and not just cMab resistance, is related to PTEN (10); therefore, there is a need to evaluate alterations of gene expression in the PI3K-AKT pathway including PTEN as a mechanism for the enhancement of antitumor effects with PTX+cMab. The collage gel droplet embedded culture drug sensitivity test (CD-DST) is an anticancer drug sensitivity test that combines a low-volume 3-dimensional (3D) culture, serum-free media, and an image colorimetric assay, and is effectively used to guide personalized treatment for lung, breast, gastric, and colorectal cancers (11); reportedly, it is also capable of evaluat...
<b><i>Objective:</i></b> A combination of the taxane anticancer drug paclitaxel (PTX) and molecular target drug cetuximab (cMab) is effective for the treatment of head and neck squamous cell carcinoma (HNSCC). However, its use is associated with serious side effects, such as neuropathy and myelosuppression. In addition, it is administered regardless of patient sensitivity because biomarkers indicating its efficacy are unavailable. Therefore, we investigated the usefulness of setting the indicated contact concentration of PTX and predicted the antitumor effect of combined contact with cMab using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST). <b><i>Method:</i></b> Twelve human oral squamous cell carcinoma (OSCC) cell lines (i.e., SAS, HSC-2, HSC-3, HSC-4, OSC-19, OSC-20, KON, HO-1-N-1, HO-1-u-1, SAT, SCC-4, and Nialym) were used. Using the CD-DST, we calculated the optimal contact concentration of the cells with PTX based on the clinical response rate of HNSCC and evaluated the combined contact with cMab. Furthermore, nude mice were treated with standalone PTX and PTX + cMab, and the results were compared with those of the CD-DST. <b><i>Results:</i></b> Based on the CD-DST, 0.1 μg/mL was the optimal contact concentration of PTX, to which the cells showed dose-dependent sensitivity. Moreover, the CD-DST method was used to evaluate the antitumor effects on OSCC even when PTX was used in combination with cMab. The antitumor effects in the CD-DST and nude mice were correlated (<i>p</i> < 0.05). <b><i>Conclusion:</i></b> The CD-DST results suggested that it was possible to predict the clinical effects of single-contact PTX and the enhancing effect of cMab + PTX.
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