Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma.
Antitumor effects of bevacizumab in combination with fluoropyrimidine drugs on human oral squamous cell carcinoma.
复制标题
DOI：
10.3892/ol.2021.12991
复制
发表时间：
2021-10
期刊：
影响因子：
2.9
通讯作者：
Mishima K
中科院分区：
文献类型：
--
作者：
Itashiki Y;Harada K;Takenawa T;Ferdous T;Ueyama Y;Mishima K
血管内皮生长因子（VEGF）在新血管形成或血管生成中发挥重要作用，这是肿瘤生长和转移的关键事件。贝伐珠单抗是一种针对 VEGF-A 的人源化单克隆抗体，而 S-1 是一种氟嘧啶类抗肿瘤药物，可诱导各种类型癌细胞的凋亡。本研究评估了贝伐珠单抗联合 5-氟尿嘧啶 (5-FU) 或 S-1 在体外和体内对口腔鳞状细胞癌 (OSCC) 的抗肿瘤作用。使用两种人 OSCC 细胞系，即高 VEGF-A 表达的 HSC-2 细胞和低 VEGF-A 表达的 SAS 细胞。 MTT法用于评估贝伐珠单抗和/或5-FU对HSC-2和SAS细胞增殖的影响。此外，还评估了贝伐珠单抗单独以及与 S-1 联合使用对裸鼠 HSC-2 肿瘤的抗肿瘤作用。每天口服S-1（6.9 mg/kg/天），持续3周，贝伐单抗（5 ml/kg/天）腹腔注射，每周两次，持续3周。采用TUNEL法检测小鼠肿瘤中的凋亡细胞，并分别通过Ki-67和CD31的免疫组化染色测定细胞增殖和微血管密度（MVD）。贝伐珠单抗单独使用在体外不抑制OSCC细胞增殖，并且在体外与5-FU联合使用时不表现出任何协同抑制作用。然而，贝伐珠单抗和S-1联合治疗对HSC-2肿瘤异种移植物在体内发挥协同且显着的抗肿瘤作用，并诱导肿瘤细胞凋亡。此外，这种联合疗法导致 MVD 和细胞增殖能力降低，以及残余肿瘤细胞凋亡增加。目前的研究结果表明，贝伐珠单抗加 S-1 联合疗法可能在高 VEGF-A 表达的 OSCC 细胞中发挥抗肿瘤作用。
Vascular endothelial growth factor (VEGF) serves an important role in new blood vessel formation or angiogenesis, which is a critical event in tumor growth and metastasis. Bevacizumab is a humanized monoclonal antibody against VEGF-A, whereas S-1 is a fluoropyrimidine antineoplastic agent that induces apoptosis in various types of cancer cells. The present study evaluated the antitumor effects of bevacizumab in combination with 5-fluorouracil (5-FU) or S-1 against oral squamous cell carcinoma (OSCC) in vitro and in vivo. Two human OSCC cell lines were used, namely the high VEGF-A-expressing HSC-2 cells and the low VEGF-A-expressing SAS cells. MTT assay was used to evaluate the effect of bevacizumab and/or 5-FU against HSC-2 and SAS cell proliferation. Additionally, the antitumor effect of bevacizumab was evaluated alone and in combination with S-1 against HSC-2 tumors in nude mice. S-1 (6.9 mg/kg/day) was administered orally every day for 3 weeks, and bevacizumab (5 ml/kg/day) was injected intraperitoneally twice per week for 3 weeks. Apoptotic cells in mouse tumors were detected using the TUNEL method, and cell proliferation and microvessel density (MVD) were determined by immunohistochemical staining of Ki-67 and CD31, respectively. Bevacizumab alone did not inhibit OSCC cell proliferation in vitro, and did not exhibit any synergistic inhibitory effect in combination with 5-FU in vitro. However, combined bevacizumab and S-1 therapy exerted synergistic and significant antitumor effects in vivo on HSC-2 tumor xenografts, and induced apoptosis in tumor cells. Furthermore, this combination therapy led to decreased MVD and cell proliferative abilities, as well as increased apoptosis in residual tumors. The present findings suggested that the bevacizumab plus S-1 combination therapy may exert antitumor effects in high VEGF-A-expressing OSCC cells.
登录
查看更多内容
影响因子：
2.3
作者：
Harada, Koji;Sato, Mitsunobu;Ryoke, Kazuo
通讯作者：
Ryoke, Kazuo
影响因子：
2.1
作者：
ROLAND, NJ;CASLIN, AW;JONES, AS
通讯作者：
JONES, AS
通过预防新血管形成，体内肿瘤休眠。
影响因子：
15.3
作者：
Gimbrone, M A Jr;Leapman, S B;Cotran, R S;Folkman, J
通讯作者：
Folkman, J
DOI：
10.1084/jem.138.4.745
发表时间：
1973-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Folkman J;Hochberg M
通讯作者：
Hochberg M
影响因子：
82.9
作者：
HOLMGREN, L;OREILLY, MS;FOLKMAN, J
通讯作者：
FOLKMAN, J