1. Academic Validation
  2. Accumulated cytotoxicity of CDK inhibitor dinaciclib with first-line chemotherapy drugs in salivary adenoid cystic carcinoma cells

Accumulated cytotoxicity of CDK inhibitor dinaciclib with first-line chemotherapy drugs in salivary adenoid cystic carcinoma cells

  • Odontology. 2020 Apr;108(2):300-311. doi: 10.1007/s10266-019-00451-5.
Laijun Xu 1 Lingzhi Li 1 Jun Zhang 2 Wenping Cai 1 Shouliang Zhao 3 Shangfeng Liu 4 5
Affiliations

Affiliations

  • 1 Department of Stomatology, Huashan Hospital, Fudan University, 12 Urumqi Road, Shanghai, 200040, People's Republic of China.
  • 2 Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
  • 3 Department of Stomatology, Huashan Hospital, Fudan University, 12 Urumqi Road, Shanghai, 200040, People's Republic of China. slzhao@fudan.edu.cn.
  • 4 Department of Stomatology, Huashan Hospital, Fudan University, 12 Urumqi Road, Shanghai, 200040, People's Republic of China. shangfengliufudan@163.com.
  • 5 Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, No. 2, Tianjing Road, Shanghai, 200001, People's Republic of China. shangfengliufudan@163.com.
Abstract

Adenoid cystic carcinoma (ACC) is one of the most common salivary gland malignant tumors. Its treatment failure is partly due to the limitations of chemotherapeutic agents and their adverse effects. The objective of this study was to determine the potential additive anti-cancer effect of a novel CDK Inhibitor dinaciclib with first-line chemotherapy drugs in ACC. Protein expression of phosphorylated CDK2 (p-CDK2) in paraffin-embedded tissue specimens of ACC from 17 patients was investigated by immunohistochemistry (IHC). Cell Counting Kit (CCK-8), clone formation assay, and flow cytometry were used to test the proliferation and Apoptosis of ACC-2 cells treated with dinaciclib with or without other first-line chemotherapy drugs. Protein expression was also determined by Western blot. Interestingly, we discovered that p-CDK2 protein was expressed in both cytoplasmic and nucleus in salivary ACC tissues, which was higher than that in normal salivary tissues, indicating that agents targeting CDK2 may be potential therapeutic strategies against this type of tumor. As expected, CDK Inhibitor dinaciclib significantly induced ACC-2 cells Apoptosis. Moreover, it sensitized cells to the chemotherapeutic agents such as cisplatin, pemetrexed, and etoposide (VP-16), and this effect by dinaciclib may induce cell cycle arrest via abrogating CDK2 activity. Therefore, combinational therapy of CDK Inhibitor dinaciclib with first-line chemotherapy drugs may be a promising strategy in the treatment of salivary ACC.

Keywords

Apoptosis; Chemotherapy; Dinaciclib; Proliferating; Salivary adenoid cystic carcinoma.

Figures
Products