Hsu Pei-Yu, Chen Jiun-Liang, Kuo Shun-Li, Wang Wan-Ling, Jan Fei-Wen, Yang Sien-Hung, Yang Chia-Yu
Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Integr Cancer Ther. 2022 Jan-Dec;21:15347354221134921. doi: 10.1177/15347354221134921.
Oral squamous cell carcinoma (OSCC) is an aggressive cancer whose 5-year survival rate remains poor. San-Zhong-Kui-Jian-Tang (SZKJT), a Chinese herbal formula, has long been used in clinical practice as adjuvant therapy in cancers. However, its therapeutic effects and molecular mechanisms in OSCC remain unclear.
We investigated the potential therapeutic effects and molecular mechanism of SZKJT in OSCC in tumor cell lines and in tumor xenograft mice and evaluated combined SZKJT and cisplatin treatment efficacy. In vitro-cultured OSCC cells were administered SZKJT at different doses or SZKJT plus cisplatin, and cell proliferation, colony formation assays, and cell cycle analysis were used to assess the effects on cancer cell proliferation and apoptosis. We also analyzed the effects of SZKJT on oral cancer cell line migration, the regulation of mitogen-activated protein kinase (MAPK) signaling, and epithelial-mesenchymal transition (EMT)-associated genes. The antitumor effects of SZKJT plus cisplatin were also tested in vivo using a tumor-bearing NOD/SCID mice model.
The results showed that SZKJT effectively inhibited OSCC cell proliferation, induced cell cycle S phase arrest, and induced cell apoptosis. SZKJT also inhibited cell migration by modulating the MAPK signaling and epithelial-mesenchymal transition (EMT) pathway. Further exploration suggested that SZKJT affects OSCC by modulating ERK pathway; downregulating vimentin, fibronectin, and Oct-4; and upregulating E-cadherin. In vivo, SZKJT significantly inhibited tumor growth, and SZKJT and cisplatin exerted synergistic antitumor effects in model animals.
SZKJT exerts antitumor effects in OSCC cells. Additionally, SZKJT and cisplatin exhibit synergy in OSCC treatment. These findings support the clinical usage of Chinese herbal formulas as adjuvant therapy with chemotherapy in cancer treatment.
口腔鳞状细胞癌（OSCC）是一种侵袭性癌症，其5年生存率仍然很低。中药方剂三忠溃坚汤（SZKJT）长期以来一直作为癌症的辅助治疗方法应用于临床实践。然而，其在OSCC中的治疗效果和分子机制仍不清楚。
我们在肿瘤细胞系和肿瘤异种移植小鼠中研究了SZKJT在OSCC中的潜在治疗效果和分子机制，并评估了SZKJT与顺铂联合治疗的疗效。将体外培养的OSCC细胞给予不同剂量的SZKJT或SZKJT加顺铂，并使用细胞增殖、集落形成试验和细胞周期分析来评估对癌细胞增殖和凋亡的影响。我们还分析了SZKJT对口腔癌细胞系迁移、丝裂原活化蛋白激酶（MAPK）信号通路的调节以及上皮-间质转化（EMT）相关基因的影响。还使用荷瘤NOD/SCID小鼠模型在体内测试了SZKJT加顺铂的抗肿瘤作用。
结果表明，SZKJT有效抑制OSCC细胞增殖，诱导细胞周期S期阻滞，并诱导细胞凋亡。SZKJT还通过调节MAPK信号通路和上皮-间质转化（EMT）途径抑制细胞迁移。进一步研究表明，SZKJT通过调节ERK途径、下调波形蛋白、纤连蛋白和Oct-4以及上调E-钙黏蛋白来影响OSCC。在体内，SZKJT显著抑制肿瘤生长，并且SZKJT和顺铂在模型动物中发挥协同抗肿瘤作用。
SZKJT在OSCC细胞中发挥抗肿瘤作用。此外，SZKJT和顺铂在OSCC治疗中表现出协同作用。这些发现支持了中药方剂作为癌症治疗中化疗辅助治疗的临床应用。
