Secondary Logo

Journal Logo

Abstracts: Abstracts of Papers Submitted to the 38th Annual Meeting of the American Pancreatic Association, November 1-3, 2007, Chicago, Illinois

TRIPTOLIDE INHIBITS TUMOR GROWTH AND LOCAL-REGIONAL SPREAD IN VIVO VIA INCREASED APOPTOSIS AND DECREASED HEAT SHOCK PROTEIN 70 (HSP70)

Phillips, P. A.; Dudeja, V.; Borja-Cacho, D.; McCarroll, J.; Dawra, R.; Grizzle, W.; Vickers, S.; Saluja, A.

Author Information
doi: 10.1097/01.mpa.0000297770.28197.06
  • Free

Introduction:

Pancreatic cancer has a high level of resistance to current chemotherapy agents. Overexpression of HSP70 in pancreatic cancer cells confers resistance to apoptosis and inhibition of HSP70 induces apoptosis in these cells.

Aims:

To examine the effect of triptolide (a diterpenoid triepoxide) on: i) pancreatic cancer cell viability and apoptosis; ii) pancreatic cancer growth and local-invasion in vivo; and iii) HSP70 levels in vitro and in vivo.

Methods:

Pancreatic cancer cells (MiaPaCa-2 and PANC-1) or normal pancreatic duct cells (PDC) were incubated with triptolide (100-200nM) or vehicle for 24h. Cell viability, apoptosis and HSP70 levels were assessed. We used an orthotopic model of pancreatic cancer by injecting MiaPaCa-2 cells into the pancreas; 6 days later we administered triptolide (0.2mg/kg/day) or vehicle for 60 days.

Results:

Triptolide significantly reduced pancreatic cancer cell viability, but had no effect on PDC viability (Triptolide 200nM - % of Control: MiaPaCa-2 56 ± 3, PANC-1 60 ± 2, PDC 85 ± 4). Triptolide induced apoptosis in the cancer cells as shown by increased Annexin V, caspase 3 (Table) and TUNEL. Triptolide decreased pancreatic cancer growth in vivo (Tumor cm3: Control 1.03 ± 0.43 vs Triptolide 0.14 ± 0.05, *p < 0.05, n ≥ 7, Mean ± SE), which was associated with increased apoptosis (TUNEL). Triptolide decreased local-regional spread (p < 0.001) to multiple organs compared to controls. Triptolide decreased HSP70 levels in vitro and in vivo compared to controls. (Table 1)

TABLE 1
TABLE 1:
Caption not available.

Conclusion:

Triptolide causes pancreatic cancer cell death via apoptosis and its mechanism of action may be mediated by the inhibition of HSP70. Triptolide is a potential therapeutic agent to prevent the progression and invasion of pancreatic cancer.

© 2007 Lippincott Williams & Wilkins, Inc.