188Re-HYNIC-trastuzumab enhances the effect of apoptosis induced by trastuzumab in HER2-overexpressing breast cancer cells

Tsai Yueh Luo, Po Ching Cheng, Ping Fang Chiang, Ting Wu Chuang, Chung Hsin Yeh, Wuu Jyh Lin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: The development of radioimmunotherapy has provided an impressive alternative approach in improving trastuzumab therapy. However, the mechanisms of trastuzumab and radiation treatment combined to increase therapeutic efficacy are poorly understood. Here, we try to examine the efficacy of cytotoxicity and apoptosis induction for 188Re-HYNIC-trastuzumab in cancer cell lines with various levels of Her2.

Materials and methods: Fluorescence flow cytometry was used to detect the alterations of apoptosis induction after 188Re-HYNIC-trastuzumab treatment in two breast cancer cell lines with different levels of HER2 (BT-474 and MCF-7) and a colorectal carcinoma cell line (HT-29) for control.

Results: Our results indicated that 188Re-HYNIC-trastuzumab led to cell death of breast cancer cells specifically in HER2 level-dependent and radioactivity dose-dependent fashions. In BT-474 cells, 370 kBq/ml of 188Re-HYNIC-trastuzumab enhanced the cytotoxicity to a level nearly 100-fold that of trastuzumab-alone treatment. The results also revealed that the mitochondria-dependent pathway attenuated irradiation-induced apoptosis in HER2-expressing breast cancer cells after 188Re-HYNIC-trastuzumab treatment. In contrast, only after 48 h of 188Re-HYNIC-trastuzumab treatment, BT-474 cells exhibited typical apoptotic changes, including exposure of phospholipid phosphatidylserine on the cell surface, or fragmented DNA formation, in a radioactivity dose-dependent manner.

Conclusion: Briefly, our study demonstrates that 188Re-labeled HYNIC-trastuzumab not only enhances cell death in a radioactivity dose-dependent fashion, but may also prolong the effects of apoptosis involved with the mitochondria-dependent pathway in HER2-overexpressing breast cancer cells. It is possible that the 188Re-HYNIC-trastuzumab treatment induced a second round of apoptosis to prolong the effects of cell kill in these cancer cells. These data revealed that 188Re-HYNIC-trastuzumab has the potential for use as a therapeutic radiopharmaceutical agent in HER2-overexpressing breast cancer cell treatment.

Original languageEnglish
Pages (from-to)52-62
Number of pages11
JournalAnnals of Nuclear Medicine
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Apoptosis
Breast Neoplasms
Radioactivity
Therapeutics
Cell Line
Trastuzumab
Mitochondria
Cell Death
Radioimmunotherapy
Radiopharmaceuticals
Phosphatidylserines
Colorectal Neoplasms
Neoplasms
Phospholipids
Flow Cytometry
Fluorescence
Radiation
DNA

Keywords

  • <sup>188</sup>Re-HYNIC-trastuzumab
  • Apoptosis
  • Breast cancer cell line
  • HER2-overexpression
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

188Re-HYNIC-trastuzumab enhances the effect of apoptosis induced by trastuzumab in HER2-overexpressing breast cancer cells. / Luo, Tsai Yueh; Cheng, Po Ching; Chiang, Ping Fang; Chuang, Ting Wu; Yeh, Chung Hsin; Lin, Wuu Jyh.

In: Annals of Nuclear Medicine, Vol. 29, No. 1, 01.01.2015, p. 52-62.

Research output: Contribution to journalArticle

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AU - Chiang, Ping Fang

AU - Chuang, Ting Wu

AU - Yeh, Chung Hsin

AU - Lin, Wuu Jyh

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N2 - Purpose: The development of radioimmunotherapy has provided an impressive alternative approach in improving trastuzumab therapy. However, the mechanisms of trastuzumab and radiation treatment combined to increase therapeutic efficacy are poorly understood. Here, we try to examine the efficacy of cytotoxicity and apoptosis induction for 188Re-HYNIC-trastuzumab in cancer cell lines with various levels of Her2.Materials and methods: Fluorescence flow cytometry was used to detect the alterations of apoptosis induction after 188Re-HYNIC-trastuzumab treatment in two breast cancer cell lines with different levels of HER2 (BT-474 and MCF-7) and a colorectal carcinoma cell line (HT-29) for control.Results: Our results indicated that 188Re-HYNIC-trastuzumab led to cell death of breast cancer cells specifically in HER2 level-dependent and radioactivity dose-dependent fashions. In BT-474 cells, 370 kBq/ml of 188Re-HYNIC-trastuzumab enhanced the cytotoxicity to a level nearly 100-fold that of trastuzumab-alone treatment. The results also revealed that the mitochondria-dependent pathway attenuated irradiation-induced apoptosis in HER2-expressing breast cancer cells after 188Re-HYNIC-trastuzumab treatment. In contrast, only after 48 h of 188Re-HYNIC-trastuzumab treatment, BT-474 cells exhibited typical apoptotic changes, including exposure of phospholipid phosphatidylserine on the cell surface, or fragmented DNA formation, in a radioactivity dose-dependent manner.Conclusion: Briefly, our study demonstrates that 188Re-labeled HYNIC-trastuzumab not only enhances cell death in a radioactivity dose-dependent fashion, but may also prolong the effects of apoptosis involved with the mitochondria-dependent pathway in HER2-overexpressing breast cancer cells. It is possible that the 188Re-HYNIC-trastuzumab treatment induced a second round of apoptosis to prolong the effects of cell kill in these cancer cells. These data revealed that 188Re-HYNIC-trastuzumab has the potential for use as a therapeutic radiopharmaceutical agent in HER2-overexpressing breast cancer cell treatment.

AB - Purpose: The development of radioimmunotherapy has provided an impressive alternative approach in improving trastuzumab therapy. However, the mechanisms of trastuzumab and radiation treatment combined to increase therapeutic efficacy are poorly understood. Here, we try to examine the efficacy of cytotoxicity and apoptosis induction for 188Re-HYNIC-trastuzumab in cancer cell lines with various levels of Her2.Materials and methods: Fluorescence flow cytometry was used to detect the alterations of apoptosis induction after 188Re-HYNIC-trastuzumab treatment in two breast cancer cell lines with different levels of HER2 (BT-474 and MCF-7) and a colorectal carcinoma cell line (HT-29) for control.Results: Our results indicated that 188Re-HYNIC-trastuzumab led to cell death of breast cancer cells specifically in HER2 level-dependent and radioactivity dose-dependent fashions. In BT-474 cells, 370 kBq/ml of 188Re-HYNIC-trastuzumab enhanced the cytotoxicity to a level nearly 100-fold that of trastuzumab-alone treatment. The results also revealed that the mitochondria-dependent pathway attenuated irradiation-induced apoptosis in HER2-expressing breast cancer cells after 188Re-HYNIC-trastuzumab treatment. In contrast, only after 48 h of 188Re-HYNIC-trastuzumab treatment, BT-474 cells exhibited typical apoptotic changes, including exposure of phospholipid phosphatidylserine on the cell surface, or fragmented DNA formation, in a radioactivity dose-dependent manner.Conclusion: Briefly, our study demonstrates that 188Re-labeled HYNIC-trastuzumab not only enhances cell death in a radioactivity dose-dependent fashion, but may also prolong the effects of apoptosis involved with the mitochondria-dependent pathway in HER2-overexpressing breast cancer cells. It is possible that the 188Re-HYNIC-trastuzumab treatment induced a second round of apoptosis to prolong the effects of cell kill in these cancer cells. These data revealed that 188Re-HYNIC-trastuzumab has the potential for use as a therapeutic radiopharmaceutical agent in HER2-overexpressing breast cancer cell treatment.

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