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Updated: Jan 31, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
PIM-1-specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation,
Xiu Feng Hu1, Jie Li, Scott Vandervalk
1Cancer Immunotherapy Laboratory, Burnet Institute Incorporating Austin Research Institute, Heidelberg, Victoria, Australia.
Abstract:
Provirus integration site for Moloney murine leukemia virus (PIM1) is a proto-oncogene that encodes a serine/threonine kinase with multiple cellular functions. Overexpression of PIM-1 plays a critical role in progression of prostatic and hematopoietic malignancies. Here we describe the generation of a mAb specific for GST-PIM-1, which reacted strongly with most human and mouse cancer tissues and cell lines of prostate, breast, and colon origin but only weakly (if at all) with normal tissues. The mAb binds to PIM-1 in the cytosol and nucleus as well as to PIM-1 on the surface of human and murine cancer cells. Treatment of human and mouse prostate cancer cell lines with the PIM-1-specific mAb resulted in disruption of PIM-1/Hsp90 complexes, decreased PIM-1 and Hsp90 levels, reduced Akt phosphorylation at Ser473, reduced phosphorylation of Bad at Ser112 and Ser136, and increased cleavage of caspase-9, an indicator of activation of the mitochondrial cell death pathway. The mAb induced cancer cell apoptosis and synergistically enhanced antitumor activity when used in combination with cisplatin and epirubicin. In tumor models, the PIM-1-specific mAb substantially inhibited growth of the human prostate cancer cell line DU145 in SCID mice and the mouse prostate cancer cell TRAMP-C1 in C57BL/6 mice. These findings are important because they provide what we believe to be the first in vivo evidence that treatment of prostate cancer may be possible by targeting PIM-1 using an Ab-based therapy.
Insights
A novel antibody targeting Provirus integration site for Moloney murine leukemia virus (PIM-1) effectively reduces prostate cancer growth in vivo. This PIM-1 antibody therapy shows promise for treating various cancers by inducing apoptosis and enhancing chemotherapy efficacy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Provirus integration site for Moloney murine leukemia virus (PIM-1) is a proto-oncogene kinase implicated in cancer progression.
- PIM-1 overexpression is critical in prostatic and hematopoietic malignancies.
Purpose of the Study:
- To generate and characterize a monoclonal antibody (mAb) specific for PIM-1.
- To evaluate the therapeutic potential of this PIM-1-specific mAb in preclinical cancer models.
Main Methods:
- Generation of a mAb against PIM-1.
- Testing mAb reactivity against human and mouse cancer tissues and cell lines.
- Assessing mAb effects on PIM-1/Hsp90 complexes, signaling pathways (Akt, Bad), and apoptosis markers (caspase-9).
- Evaluating in vivo efficacy in prostate cancer xenograft and syngeneic mouse models, alone and in combination with chemotherapy.
Main Results:
- The PIM-1 mAb showed high specificity for cancer tissues and cell lines.
- mAb treatment disrupted PIM-1/Hsp90 complexes, reduced PIM-1/Hsp90 levels, and inhibited pro-survival signaling.
- The mAb induced cancer cell apoptosis and synergistically enhanced antitumor activity with cisplatin and epirubicin.
- In vivo studies demonstrated substantial inhibition of prostate cancer growth by the PIM-1 mAb.
Conclusions:
- The PIM-1-specific mAb is a promising therapeutic agent for prostate cancer.
- This study provides the first in vivo evidence for Ab-based therapy targeting PIM-1 in cancer treatment.
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