Optimal Contact Concentration of Paclitaxel in the Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test for Human Oral Squamous Cell Carcinoma and Evaluation of Combination with Cetuximab

Chemotherapy ◽  
2020 ◽  
Vol 65 (5-6) ◽  
pp. 147-157
Author(s):  
Tomoyuki Kii ◽  
Kaname Sakuma ◽  
Akira Tanaka

<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> &#x3c; 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.

2020 ◽  
Author(s):  
Fazhan Wang ◽  
Jun Zheng ◽  
Yongyong Yang ◽  
Jie Yang ◽  
Ting Luo ◽  
...  

Abstract Background Naa10p (N-α-Acetyltransferase 10 protein) was reported to be involved in tumor invasion and metastasis in several of tumors. However, the role and mechanism of Naa10p mediated invasion and metastasis in oral squamous cell carcinoma (OSCC) remains undetermined. Methods The functional role of Naa10p in OSCC cells were determined using Transwell assay in vitro and xenograft tumorigenesis in nude mice. Immunoprecipitation, GST-pull down assays and immunofluorescence were performed to confirm the interaction between Naa10p and RelA/p65 in OSCC cells. Lastly, luciferase reporter assays, chromatin immunoprecipitation (ChIP) and western blot were used to evalute the effect of Naa10p expression on the Pirh2-p53 signaling pathway. Results Naa10p inhibits cell migration and invasion in vitro and attenuates the xenograft tumorigenesis in nude mice. Mechanistically, there is a physical interaction between Naa10p and RelA/p65 in OSCC cells, thereby preventing RelA/p65-mediated transcriptional activation of Pirh2. Consequently, inhibition of Pirh2 increased p53 level and suppressed the expression of p53 downstream targets, MMP-2 and MMP-9. Conclusion Naa10p function as a tumor metastasis suppressor in the progression of OSCC by targeting Pirh2-p53 axis, and might be a prognostic marker as well as a therapeutic target for OSCC.


2020 ◽  
Vol 40 (9) ◽  
pp. 4885-4894
Author(s):  
MICHITO TERATANI ◽  
SHOUTA NAKAMURA ◽  
HIROSHI SAKAGAMI ◽  
MASAKAZU FUJISE ◽  
MASASHI HASHIMOTO ◽  
...  

2021 ◽  
Vol 22 (4) ◽  
Author(s):  
Yasutaka Itashiki ◽  
Koji Harada ◽  
Takanori Takenawa ◽  
Tarannum Ferdous ◽  
Yoshiya Ueyama ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e98885 ◽  
Author(s):  
Juan Wang ◽  
Lihua Jia ◽  
Zirong Kuang ◽  
Tong Wu ◽  
Yun Hong ◽  
...  

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