Cited by 10Lymphoma Diagnosis and TreatmentChronic Lymphocytic Leukemia ResearchAutophagy in Disease and Therapy

Metronomic Combination Chemotherapy Using Everolimus and Etoposide for the Treatment of non‐Hodgkin Lymphoma

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Wu, Ke, Sun, Xiao‐Qing, Wang, Cai‐Qin, Gao, Tian‐Xiao, Sun, Peng, Wang, Yu, Jiang, Wen‐Qi, Li, Zhi‐Ming +1 more·2019·Cancer Medicine

Abstract

Patients with Non-Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination chemotherapy (MCC) enhances therapeutic efficacy and decreases side effects in the treatment of NHL. In this study, we tested and compared the effects of metronomic chemotherapy (MC) using podophyllotoxin derivative etoposide (VP-16) alone and that of MCC using both VP-16 and everolimus (RAD001) in the treatment of NHL. Two types of NHL cells, OCI-LY-10 and SU-DHL-6, were employed for the experiments. Cell proliferation, apoptosis, and cell senescence were measured to test the effects of drugs in each experiment. In addition, the influences of MC and MCC on the cell cycle and autophagy pathway were evaluated to study the functional mechanisms behind their effects. Finally, we conducted analyses of the growth inhibitory effect and synergistic activity for different MCC. The results showed that MC using low-dose VP-16 alone demonstrated strong treatment effects in terms of inducing apoptosis, cell senescence, and reducing tumor cell proliferation, and this treatment also led to changes of the cell cycle. Compared with MC, MCC using VP-16 and RAD001 together demonstrated even stronger treatment effects, with both the cell cycle and autophagy-related proteins being affected. Considering the synergistic activity, our results showed the MCC of VP-16 48 hours + RAD001 24 hours is the optimal method for treating NHL.

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Authors
Wu, K., Sun, X., Wang, C., Gao, T., Sun, P., Wang, Y., Jiang, W., Li, Z., & Huang, J.
Affiliations
  • Sun Yat-sen University (CN)
  • Department of Medical Oncology, Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou China
Venue
Cancer Medicine
Publisher
Wiley
Published
2019-06-20
Volume
8
Issue
10
Pages
4688-4698
ISSN
2045-7634 (ISSN-L)
OpenAlex
W2951823164
Cited by
10
References
39
Citations by year
2025: 1 · 2024: 2 · 2022: 1 · 2021: 4 · 2020: 2
FWCI
1.29
Type
journal article
Language
en
Open access
Locations
  • Cancer Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81472759, 81611130086, 81872902)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
non-Hodgkin lymphoma, metronomic chemotherapy, combination chemotherapy, everolimus, etoposide, podophyllotoxin derivatives, apoptosis, cellular senescence, cell cycle, autophagy, drug synergy
MeSH terms
Everolimus, Autophagy-Related Proteins, Antineoplastic Combined Chemotherapy Protocols, Cell Survival, Drug Synergism, Etoposide, Humans, Lymphoma, Non-Hodgkin, Gene Expression Regulation, Neoplastic, Survival Analysis, Treatment Outcome, Cell Line, Tumor, Cell Proliferation, Administration, Metronomic

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