PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) augments the therapeutic effect of pegfilgrastim on gemcitabine-induced neutropenia.
Granulocyte colony-stimulating factor (G-CSF) is widely used for preventing neutropenia during chemotherapy. Polyethylene glycol-conjugated granulocyte colony-stimulating factor (PEG-G-CSF, pegfilgrastim) serves the same purpose but has a longer half-life and greater stability than G-CSF. In this study, we investigated whether 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride (PLAG), augments the therapeutic effect of pegfilgrastim on chemotherapy-induced neutropenia. We compared neutrophil counts in four groups of mice: control mice, gemcitabine-treated mice, gemcitabine/pegfilgrastim-treated mice, and gemcitabine/pegfilgrastim/PLAG-treated mice. PLAG (50 mg/kg) was orally administered every day during the treatment course. CBC analysis showed that the group treated with PLAG experienced a dramatically increased neutrophil counts on the third day following pegfilgrastim treatment. PLAG had no effect on blood cell apoptosis and neutrophil release from bone marrow. Additionally, pegfilgrastim-induced CXCR2 expression in neutrophils was markedly decreased in PLAG-treated animals. These results suggest that PLAG plays a role in inhibiting neutrophil extravasation, giving rise to an increased number of circulating neutrophils when used with pegfilgrastim during gemcitabine treatment. These data support the potential for PLAG to be used with pegfilgrastim to treat or prevent chemotherapy-induced neutropenia by modulating neutrophil transmigration.
Cell Factory Research Center, Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea; ENZYCHEM Lifesciences, 103-6, KAIST-ICC F741, Munjidong, Daejeon 305-732, Republic of Korea.
Nina
N
Yoo
Cell Factory Research Center, Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; ENZYCHEM Lifesciences, 103-6, KAIST-ICC F741, Munjidong, Daejeon 305-732, Republic of Korea.
Ha-Reum
HR
Lee
Cell Factory Research Center, Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Su-Hyun
SH
Shin
ENZYCHEM Lifesciences, 103-6, KAIST-ICC F741, Munjidong, Daejeon 305-732, Republic of Korea.
Ki-Young
KY
Sohn
ENZYCHEM Lifesciences, 103-6, KAIST-ICC F741, Munjidong, Daejeon 305-732, Republic of Korea.
Heung-Jae
HJ
Kim
ENZYCHEM Lifesciences, 103-6, KAIST-ICC F741, Munjidong, Daejeon 305-732, Republic of Korea.
Yong-Hae
YH
Han
ENZYCHEM Lifesciences, 103-6, KAIST-ICC F741, Munjidong, Daejeon 305-732, Republic of Korea.
Saeho
S
Chong
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Myung-Hwan
MH
Kim
ENZYCHEM Lifesciences, 103-6, KAIST-ICC F741, Munjidong, Daejeon 305-732, Republic of Korea. Electronic address: syyoon@enzychem.com.
Sun Young
SY
Yoon
Cell Factory Research Center, Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea. Electronic address: wjkim@kribb.re.kr.
Jae Wha
JW
Kim
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002465:Cell Movement / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives*; D004075:Diglycerides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007958:Leukocyte Count; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011092:Polyethylene Glycols; D023063:Receptors, Interleukin-8B / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D000093542:Gemcitabine
C488567:1-palmitoyl-2-linoleoyl-3-acetyl-rac glycerol; D015415:Biomarkers; D004075:Diglycerides; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins; D003841:Deoxycytidine; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim; D000093542:Gemcitabine
Diacylglycerol; G-CSF; Gemcitabine; Neutropenia; Pegfilgrastim