Wiley

Hypoxia-inducible factor-1alpha (HIF-1α) is aberrantly upregulated in tumors and implicated in angiogenesis, metastasis, and drug resistance. Therefore, developing treatments that target HIF-1α may be a viable therapeutic approach. In Traditional Chinese Medicine (TCM), Scutellaria baicalensis (SB) is used for the treatment of cancer but the anti-cancer mechanisms are not known. We examined the effects of SB on HIF-1α expression in ovarian cancer (OC) cell lines grown under normoxic and hypoxic conditions. SB treatment attenuated HIF-1α expression in cancer cell lines. Treatment of cells with cycloheximide (CHX) reduced HIF-1α levels similar to cells treated with SB. Furthermore, SB-induced HIF-1α inhibition was abrogated by the proteasomal inhibitor MG132 and a lysosome inhibitor, chloroquine. Activation of PI3K/AKT and MAPK/ERK seen in OC cells was reduced with SB. Pretreatment of cells with LY294002 (phosphoinositide 3-kinase inhibitor) and PD98059 (mitogen-activated protein kinase inhibitor) reduced HIF-1α expression comparable to SB-treated cells. SB potentiated the anti-growth effects of cisplatin on OC cells by attenuating the expression of HIF-1α, ABCG1, and ABCG2. Taken together, the findings suggest that targeting HIF-1α with SB could be an effective treatment strategy for cancer and SB can improve the sensitivity of cancer cells to cisplatin, which is a major challenge in therapy for ovarian tumors.

Objective: Back and neck pain are associated with disability and loss of independence in older adults. Whether long-term management using commonly recommended treatments is superior to shorter-term treatment is unknown. This randomized clinical trial compared short-term treatment (12 weeks) versus long-term management (36 weeks) of back- and neck-related disability in older adults using spinal manipulative therapy (SMT) combined with supervised rehabilitative exercises (SRE).

Methods: Eligible participants were ages ≥65 years with back and neck disability for ≥12 weeks. Coprimary outcomes were changes in Oswestry Disability Index (ODI) and Neck Disability Index (NDI) scores after 36 weeks. An intent-to-treat approach used linear mixed-model analysis to detect between-group differences. Secondary analyses included other self-reported outcomes, adverse events, and objective functional measures.

Results: A total of 182 participants were randomized. The short-term and long-term groups demonstrated significant improvements in back disability (ODI score –3.9 [95% confidence interval (95% CI) –5.8, –2.0] versus ODI score –6.3 [95% CI –8.2, –4.4]) and neck disability (NDI score –7.3 [95% CI –9.1, –5.5] versus NDI score –9.0 [95% CI –10.8, –7.2]) after 36 weeks, with no difference between groups (back ODI score 2.4 [95% CI –0.3, 5.1]; neck NDI score 1.7 [95% CI 0.8, 4.2]). The long-term management group experienced greater improvement in neck pain at week 36, in self-efficacy at weeks 36 and 52, and in functional ability, and balance.

Conclusion: For older adults with chronic back and neck disability, extending management with SMT and SRE from 12 to 36 weeks did not result in any additional important reduction in disability.