Zoledronic acid (ZA), a nitrogen-containing bisphosphonate with established clinical utility in osteoporosis management, exhibits emerging antitumor potential in estrogen receptor-positive breast cancer. However, the molecular mechanisms underlying its nonapoptotic anticancer effects remain poorly characterized. This study revealed that ZA induced ferroptosis in ER+ breast cancer cells through dual suppression of cystine-glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4), key repressors of ferroptosis. Pharmacological inhibition of ferroptosis using Ferrostatin-1 significantly attenuated ZA-induced cytotoxicity, while combinatorial treatment with the GPX4 inhibitor RSL3 synergistically enhanced lipid peroxidation and cell death. Mechanistically, ZA activated the Hippo-YAP signaling pathway, promoting YAP phosphorylation, proteasomal degradation, and cytoplasmic retention, thereby silencing SLC7A11 and GPX4. We established a novel metabolic vulnerability in hormone-responsive malignancies.These findings position ZA as a bifunctional ferroptosis inducer in ER+ breast cancer, offering a promising strategy to overcome endocrine resistance.

Objective: To analyze the clinical features of perianal condyloma acuminatum in HIV infected men who have sex with men (MSM) and assess the effects of combined treatment of microwave and photodynamic therapy. Methods: Clinical and laboratory data of 260 male patients with perianal condyloma acuminatum were collected and microwave combined with photodynamic therapy was applied on them. Results: The majority of the patients with perianal condyloma acuminatum were young people (243/260). Warts were mainly located in the anus or from the outside to inside of the anus (245/260). Among them, the proportion of warts position of extraanal in HIV-infected group (8/220) was lower than that of non-HIV-infected group (7/40). HPV types 11 (70/118), 6 (44/118) and 16 (40/118) were the most common types of HPV infection. People with HIV infection were more likely to develop high-risk, mixed types HPV infection and multiple HPV infection than those without HIV infection. More than half of the patients (146/260) needed only 1-3 sessions of photodynamic treatments. There was no significant difference in the times of photodynamic treatments and the numbers of photosensitizers required between the HIV-infected and non-HIV-infected groups. The recurrence rate of HIV-infected group (13.6%, 30/220) was also similar to that of non-HIV-infected group (15.0%, 6/40), but far lower than those who underwent microwave therapy alone (45%, 18/40). Conclusions The combination therapy significantly reduced the recurrence rate of perianal condyloma acuminatum in HIV infected MSM.