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Tumor Discovery HHT inhibits pancreatic cancer progress

p53 and checkpoint protein kinases checkpoint kinase 026), Haihe Laboratory of Cell Ecosystem Innovation
1 (CHK1) and checkpoint kinase 2 (CHK2) regulate the Fund (22HHXBSS00040) and Beijing Natural Science
phosphorylation of CDC25c, inhibiting its activity during Foundation (7244372).
DNA damage. This results in the breakdown of CDC25c
in the cytoplasm, prevents the activation of the cyclin Conflict of interest
B1/CDK1 complex, and induces G2/M phase cell cycle The authors declare they have no competing interests.
arrest. 35-37 In this study, the downregulation of mp53 by
HHT treatment may be associated with its impact on cell Author contributions
cycle proteins.
Conceptualization: Haiyan Xu
Moreover, pancreatic cancer is well-known for its Formal analysis: Xiaoxia Wang
characteristic immunosuppressive TME, which includes a Funding acquisition: Haiyan Xu
large population of macrophages and fibroblasts. This study Methodology: Xiaoxia Wang, Tao Wang, Jie Meng, Xuelu
revealed that macrophages were more sensitive to HHT Peng, Ke Zhu, Ming Ye
than PANC-1 cells, suggesting that HHT might alleviate Project administration: Haiyan Xu
the TME. Tumor-associated macrophages are widely Resources: Haiyan Xu
recognized for their role in facilitating the TME, 38,39 which Supervision: Haiyan Xu
may contribute to the inhibitory effect of HHT on pancreatic Validation: Xiaoxia Wang, Tao Wang
cancer progression. In addition, this effect may promote the Writing – original draft: Jie Meng, Xiaoxia Wang
therapeutic efficacy of pancreatic cancer treatments when Writing – review & editing: Haiyan Xu, Tao Wang
combined with other existing drugs. Although no clear
mechanisms have been established, prior investigations have Ethics approval and consent to participate
shown signs of HHT sensitizing other chemotherapeutic All the animal experiments reported were carried out in
drugs in immunosuppressive cancers. For example, HHT accordance with the guidelines stipulated by the committee
acts synergistically with paclitaxel to combat triple-negative on the Animal Care and Use of Institute of Basic Medical
breast cancer cell lines and sensitizes resistant human Sciences, Chinese Academy of Medical Sciences and
40
colorectal carcinoma cells to tumor necrosis factor-related Peking Union Medical College (Ethics Approval ID:
apoptosis-inducing ligand-induced apoptosis. 41 ACUC-A02-2023-015). Mice were euthanized using
cervical dislocation following isoflurane anesthesia, in
5. Conclusion accordance with the 2020 AVMA Guidelines for the
HHT showed potent antiproliferative effects on pancreatic Euthanasia of Animals to ensure humane treatment.
cancer by inducing ROS elevation, impairing mitochondrial
energy metabolism, and causing cell cycle arrest. In Consent for publication
addition, it reduced macrophages in the TME to alleviate Not applicable.
the immunosuppressive status. These findings suggest that
HHT could potentially serve as a novel therapeutic agent for Availability of data
this devastating disease. Investigating the long-term effects The datasets used and analyzed during the current study are
of HHT on PDAC relapse and its efficacy in combination available from the corresponding author upon reasonable
with other existing drugs is worthy of future studies. request.
Acknowledgments References

The confocal microscopy was performed at the Core Labs, 1. Cai J, Chen H, Lu M, et al. Advances in the epidemiology
Institute of Basic Medical Sciences Chinese Academy of pancreatic cancer: Trends, risk factors, screening, and
of Medical Sciences. The optical small animal imaging prognosis. Cancer Lett. 2021;520:1-11.
was performed at the State Key Laboratory of Common doi: 10.1016/j.canlet.2021.06.027
Mechanism Research of Major Disease Platform. We
would like to thank the lab personnel for their help in data 2. Bray F, Laversanne M, Sung H, et al. Global cancer statistics
collection. 2022: GLOBOCAN estimates of incidence and mortality
worldwide for 36 cancers in 185 countries. CA Cancer J Clin.
Funding 2024;74(3):229-263.

This work was supported by CAMS Innovation doi: 10.3322/caac.21834
Fund for Medical Science (CIFMS 2021-I2M-1- 3. Connor AA, Gallinger S. Pancreatic cancer evolution and

Volume 4 Issue 1 (2025) 110 doi: 10.36922/td.7825