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Updated: Apr 6, 2026
Multianimal Magnetic Resonance Imaging for Tumor Measurements in Pancreatic Cancer Mouse Models
Published on: February 3, 2026
Targeted nuclear factor-kappaB suppression enhances gemcitabine response in human pancreatic tumor cell line murine
Joshua A Waters1, Jesus Matos1, Michele Yip-Schneider1
1Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.
Background:
Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly fatal malignancy characterized by resistance to chemotherapy. Currently, gemcitabine is the agent used most commonly but demonstrates only a partial response. The transcription factor nuclear factor-kappaB (NF-κB), known to be involved in the inflammatory response, is constitutively activated in PDAC and further activated by gemcitabine. Our aim was to examine the effects of targeted NF-κB suppression on gemcitabine resistance using an in vivo tumor growth model.
Methods:
To suppress the NF-κB pathway, the mutant IκBα super-repressor protein was stably expressed in PaCa-2 human PDAC cells. Athymic mice were injected subcutaneously with IκBα-super-repressor (SR) or vector-expressing PaCa-2 cells and randomized to receive phosphate-buffered saline (PBS) or 100 mg/kg gemcitabine(gem) for 4 weeks.
Results:
The mean increase in tumor volume was 47 mm(3) (89%) and 196 mm(3) (326%) in gem/SR and gem/vector groups, respectively (P = .03). The PBS-treated groups demonstrated greater tumor growth, ∼340 mm(3) (850%) increase, in both PBS/vector and PBS/SR groups. Intratumoral NF-κB activity was decreased in gem/SR compared with the gem/vector group (P = .04). Decreased Ki-67 positivity was noted in gem/SR (49%) versus gem/vector tumors (73%) (P = .04), with no difference in apoptosis (apoptag, P = .3) or angiogenesis (CD31+, P = .9).
Conclusion:
Stable IκBα-SR expression in vivo potentiated the antitumor effects of gemcitabine, resulting in decreased tumor growth in association with decreased cell proliferation. Molecular suppression of the NF-κB pathway decreases successfully gemcitabine resistance in a relatively chemoresistant PDAC line. Thus, NF-κB-targeted agents may complement gemcitabine-based therapies and decrease chemoresistance in patients with PDAC.
Insights
Targeting nuclear factor-kappaB (NF-κB) with IκBα-SR potentiated gemcitabine therapy, reducing tumor growth and cell proliferation in pancreatic cancer. This approach may overcome gemcitabine resistance in patients with pancreatic ductal adenocarcinoma (PDAC).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with significant chemotherapy resistance.
- Nuclear factor-kappaB (NF-κB) is constitutively active in PDAC and contributes to gemcitabine resistance.
Purpose of the Study:
- To investigate the efficacy of suppressing the NF-κB pathway to overcome gemcitabine resistance in PDAC.
- To evaluate the impact of targeted NF-κB inhibition on tumor growth in an in vivo model.
Main Methods:
- Stably expressed a mutant IκBα super-repressor (SR) in PaCa-2 PDAC cells to inhibit NF-κB.
- Injected mice with SR or vector-expressing cells and treated with gemcitabine or phosphate-buffered saline (PBS).
- Monitored tumor volume, NF-κB activity, cell proliferation (Ki-67), apoptosis, and angiogenesis.
Main Results:
- Gemcitabine treatment combined with IκBα-SR significantly reduced tumor volume increase compared to gemcitabine with vector (47 mm³ vs. 196 mm³).
- Intratumoral NF-κB activity and cell proliferation (Ki-67) were significantly decreased in the gemcitabine/IκBα-SR group.
- No significant differences were observed in apoptosis or angiogenesis between groups.
Conclusions:
- In vivo suppression of the NF-κB pathway potentiates gemcitabine's antitumor effects in PDAC by reducing cell proliferation.
- Targeting NF-κB may be a viable strategy to decrease gemcitabine resistance in patients with PDAC.
- NF-κB-targeted agents could complement current gemcitabine-based therapies for pancreatic cancer.
