<p>Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer</p>

Abstract

Introduction: Although the survival rate of colorectal cancer (CRC) patients can be improved by surgery, radiotherapy, and chemotherapy, the resistance to 5-fluorouracil (5-Fu) affects the effect of chemotherapy and the prognosis of patients. An increasing number of studies showed that 5-Fu resistance was the main reason for the failure of colorectal cancer treatment. The poor prognosis of colorectal cancer greatly harms people's health. This study aimed to clarify the correlation between cyclin-dependent kinase 1 (CDK1) and 5-Fu-induced tumor resistance. Materials and Methods: Cell proliferation and invasion experiments showed that downregulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation. The expression level of CDK1 was detected in 5-Fu-resistant CRC cells in vitro. Tumor growth was inhibited by down-regulation of CDK1 in tumor xenograft mouse models. Results: We found that CDK1 was highly expressed in tumor tissues, especially in fluorouracil-resistant tissues. We also confirmed that the differential expression of 5-Fu in tumor tissues was related to tumor site, lymph node metastasis and stage. CDK1 promoted migration, invasion and inhibited apoptosis in 5-Fu-resistant CRC cells. Down-regulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation and tumorigenesis in vivo. Conclusion: High expression of CDK1 may lead to poor clinical prognosis, and inhibition of CDK1 enhances 5-Fu sensitivity in CRC. Our research suggested that CDK1 may be used to predict 5-Fu efficacy and as a therapeutic target for CRC.

Identification of 5 Hub Genes Related to the Early Diagnosis, Tumour Stage, and Poor Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis

“…The research by Yang et al [ 37 ] confirms that CDK1 is associated with cancer growth and the survival rate of epithelial ovarian cancer. Recent findings [ 38 ] show that CDK1 affects 5-Fu resistance in colorectal cancer. Moreover, another study reported that the CDK1/CCNB1 axis can regulate hepatocarcinogenesis [ 39 ].…”

Cyclin-Dependent Kinase Inhibitors and Their Therapeutic Potential in Colorectal Cancer Treatment

“…The evaluation of nuclear/cytoplasm (N/C) ratio on these samples showed that high N/C expression is often found in patients with overall worse survival and a N/C > 1.5 can be considered a risk factor. Furthermore, high CDK1 expression is predominant in patients with resistance to 5-fluorouracil (5-Fu), a common CRC treatment, and it seems to reduce the effect of chemotherapy ( Zhu et al, 2020 ). An upregulation of CDK1 in CRC has been also observed in response to other drugs such as: betaxol, penbutolol and propofol amongst others ( Mastrogamvraki and Zaravinos, 2020 ).…”

Cyclin Dependent Kinase-1 (CDK-1) Inhibition as a Novel Therapeutic Strategy against Pancreatic Ductal Adenocarcinoma (PDAC)

“…However, when this cell cycle checkpoint evasion is blocked by CDK1 inhibitors, the cancer cells are less likely to survive (Figure 6). This also explains studies demonstrating that CDK1 inhibition reduces gemcitabine-and 5-FU resistance in multiple different cancer types [73,[80][81][82]. Another study showed that CDK1 inhibition enhanced the ability of the protein kinase inhibitor sorafenib to specifically kill stem cells of hepatocellular carcinoma [41].…”