Abstract

Background: Osteosarcoma (OS) is the most common and most aggressive primary solid malignant bone tumor in children and young adults and has high rates of recurrence and metastasis. The endoplasmic reticulum (ER) stress pathway is important in regulating the chemo-responsiveness of cancer. However, the role of glucose-regulated protein 94 (GRP94) in regulating the response of OS to chemotherapy has never been explored. Methods: In this study, two OS cell lines, MG63 and 143B cells, were used to evaluate the mechanism by which GRP94 modulates the response of osteosarcoma to chemotherapy. GRP94-knockdown (GRP94-KD) OS cells were generated using short hairpin RNAs, and the response to chemotherapy was assessed using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was quantified with propidium iodide (PI) staining and flow cytometry. Results: Silencing of GRP94 in MG63 and 143B cells did not influence the growth and migration of the cells, but reduced the colony formation. GRP94-KD OS cells were more resistant to paclitaxel, gemcitabine, and epirubicin treatments than cells transfected with the scrambled control, and more cells transfected with the scrambled control underwent apoptosis after paclitaxel, gemcitabine, and epirubicin treatments than GRP94-KD cells. Conclusions: Therefore, GRP94 silencing may increase the resistance of MG63 and 143B cells to paclitaxel, gemcitabine, and epirubicin treatments by inhibiting the induction of apoptosis. Thus, GRP94 may be a key biomarker for the chemotherapeutic response of OS.

Original languageEnglish
Number of pages1
JournalDisease Markers
Volume2019
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Chemotherapy
Osteosarcoma
gemcitabine
Drug Therapy
Epirubicin
Paclitaxel
Apoptosis
Cells
Flow cytometry
glucose-regulated proteins
Propidium
Endoplasmic Reticulum Stress
Biomarkers
Small Interfering RNA
Tumors
Assays
Bone
Cell Movement
Young Adult
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Glucose-Regulated Protein 94 Modulates the Response of Osteosarcoma to Chemotherapy. / Huang, Chien Yu; Wei, Po Li; Wang, Jin Wun; Makondi, Precious Takondwa; Huang, Ming Te; Chen, Hsin An; Chang, Yu Jia.

In: Disease Markers, Vol. 2019, 01.01.2019.

Research output: Contribution to journalArticle

@article{708b2649d0134d6295599ac9f85f4190,
title = "Glucose-Regulated Protein 94 Modulates the Response of Osteosarcoma to Chemotherapy",
abstract = "Background: Osteosarcoma (OS) is the most common and most aggressive primary solid malignant bone tumor in children and young adults and has high rates of recurrence and metastasis. The endoplasmic reticulum (ER) stress pathway is important in regulating the chemo-responsiveness of cancer. However, the role of glucose-regulated protein 94 (GRP94) in regulating the response of OS to chemotherapy has never been explored. Methods: In this study, two OS cell lines, MG63 and 143B cells, were used to evaluate the mechanism by which GRP94 modulates the response of osteosarcoma to chemotherapy. GRP94-knockdown (GRP94-KD) OS cells were generated using short hairpin RNAs, and the response to chemotherapy was assessed using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was quantified with propidium iodide (PI) staining and flow cytometry. Results: Silencing of GRP94 in MG63 and 143B cells did not influence the growth and migration of the cells, but reduced the colony formation. GRP94-KD OS cells were more resistant to paclitaxel, gemcitabine, and epirubicin treatments than cells transfected with the scrambled control, and more cells transfected with the scrambled control underwent apoptosis after paclitaxel, gemcitabine, and epirubicin treatments than GRP94-KD cells. Conclusions: Therefore, GRP94 silencing may increase the resistance of MG63 and 143B cells to paclitaxel, gemcitabine, and epirubicin treatments by inhibiting the induction of apoptosis. Thus, GRP94 may be a key biomarker for the chemotherapeutic response of OS.",
author = "Huang, {Chien Yu} and Wei, {Po Li} and Wang, {Jin Wun} and Makondi, {Precious Takondwa} and Huang, {Ming Te} and Chen, {Hsin An} and Chang, {Yu Jia}",
year = "2019",
month = "1",
day = "1",
doi = "10.1155/2019/4569718",
language = "English",
volume = "2019",
journal = "Disease Markers",
issn = "0278-0240",
publisher = "IOS Press",

}

TY - JOUR

T1 - Glucose-Regulated Protein 94 Modulates the Response of Osteosarcoma to Chemotherapy

AU - Huang, Chien Yu

AU - Wei, Po Li

AU - Wang, Jin Wun

AU - Makondi, Precious Takondwa

AU - Huang, Ming Te

AU - Chen, Hsin An

AU - Chang, Yu Jia

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Osteosarcoma (OS) is the most common and most aggressive primary solid malignant bone tumor in children and young adults and has high rates of recurrence and metastasis. The endoplasmic reticulum (ER) stress pathway is important in regulating the chemo-responsiveness of cancer. However, the role of glucose-regulated protein 94 (GRP94) in regulating the response of OS to chemotherapy has never been explored. Methods: In this study, two OS cell lines, MG63 and 143B cells, were used to evaluate the mechanism by which GRP94 modulates the response of osteosarcoma to chemotherapy. GRP94-knockdown (GRP94-KD) OS cells were generated using short hairpin RNAs, and the response to chemotherapy was assessed using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was quantified with propidium iodide (PI) staining and flow cytometry. Results: Silencing of GRP94 in MG63 and 143B cells did not influence the growth and migration of the cells, but reduced the colony formation. GRP94-KD OS cells were more resistant to paclitaxel, gemcitabine, and epirubicin treatments than cells transfected with the scrambled control, and more cells transfected with the scrambled control underwent apoptosis after paclitaxel, gemcitabine, and epirubicin treatments than GRP94-KD cells. Conclusions: Therefore, GRP94 silencing may increase the resistance of MG63 and 143B cells to paclitaxel, gemcitabine, and epirubicin treatments by inhibiting the induction of apoptosis. Thus, GRP94 may be a key biomarker for the chemotherapeutic response of OS.

AB - Background: Osteosarcoma (OS) is the most common and most aggressive primary solid malignant bone tumor in children and young adults and has high rates of recurrence and metastasis. The endoplasmic reticulum (ER) stress pathway is important in regulating the chemo-responsiveness of cancer. However, the role of glucose-regulated protein 94 (GRP94) in regulating the response of OS to chemotherapy has never been explored. Methods: In this study, two OS cell lines, MG63 and 143B cells, were used to evaluate the mechanism by which GRP94 modulates the response of osteosarcoma to chemotherapy. GRP94-knockdown (GRP94-KD) OS cells were generated using short hairpin RNAs, and the response to chemotherapy was assessed using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was quantified with propidium iodide (PI) staining and flow cytometry. Results: Silencing of GRP94 in MG63 and 143B cells did not influence the growth and migration of the cells, but reduced the colony formation. GRP94-KD OS cells were more resistant to paclitaxel, gemcitabine, and epirubicin treatments than cells transfected with the scrambled control, and more cells transfected with the scrambled control underwent apoptosis after paclitaxel, gemcitabine, and epirubicin treatments than GRP94-KD cells. Conclusions: Therefore, GRP94 silencing may increase the resistance of MG63 and 143B cells to paclitaxel, gemcitabine, and epirubicin treatments by inhibiting the induction of apoptosis. Thus, GRP94 may be a key biomarker for the chemotherapeutic response of OS.

UR - http://www.scopus.com/inward/record.url?scp=85061153284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061153284&partnerID=8YFLogxK

U2 - 10.1155/2019/4569718

DO - 10.1155/2019/4569718

M3 - Article

VL - 2019

JO - Disease Markers

JF - Disease Markers

SN - 0278-0240

ER -